Non-steroidal farnesoid X receptor modulators and methods for the use thereof

ABSTRACT

The efficient regulation of cholesterol synthesis, metabolism, acquisition, and transport is an essential component of lipid homeostasis. The farnesoid X receptor (FXR) is a transcriptional sensor for bile acids, the primary product of cholesterol metabolism. Accordingly, the development of potent, selective, small molecule agonists, partial agonists, and antagonists of FXR would be an important step in further deconvoluting FXR physiology. In accordance with the present invention, the identification of novel potent FXR activators is described. Two derivatives of invention compounds, bearing stilbene or biaryl moieties, contain members that are the most potent FXR agonists reported to date in cell-based assays. These compounds are useful as chemical tools to further define the physiological role of FXR as well as therapeutic leads for the treatment of diseases linked to cholesterol, bile acids and their metabolism and homeostasis.

FIELD OF THE INVENTION

The present invention relates to new chemical entities. In a particularaspect, the present invention relates to non-steroidal modulators offarnesoid X receptors (FXR). In another aspect, the present inventionrelates to methods for modulating FXR-mediated processes employing thenovel compounds described herein.

BACKGROUND OF THE INVENTION

The following discussion of the background of the invention is merelyprovided to aid the reader in understanding the invention and is notadmitted to describe or constitute prior art to the present invention.

The efficient regulation of cholesterol biosynthesis, metabolism,acquisition and transport is an essential function of mammalian cells.High levels of cholesterol are associated with atherosclerosis, aleading cause of death in the western world and a major risk factorcorrelated with the occurrence of coronary heart disease and stroke.Until recently, recommendations for the treatment of hypercholestemiawere focused on the use of statins, which inhibit the de novobiosynthesis of cholesterol, and the use of bile acid sequesteringagents. While statin-based agents are still in widespread use ascholesterol-lowering drugs, an evolving understanding of the mechanismscontrolling cholesterol homeostasis has led to new molecular targets ascandidates in therapeutic intervention.

Cholesterol metabolism is controlled through a complex feedback loopinvolving cholesterol itself and bile acids (which are primary oxidationproducts), and through secretion in the gut, the single most criticalregulators of cholesterol absorption. The nuclear receptors LXR (liver Xreceptor) and FXR (farnesoid X receptor) are the specialized sensors ofcholesterol and bile acids that control transcription of networksencoding key metabolic enzymes. For example activation of LXR byoxysterols (i.e., mono-oxygenated cholesterol metabolites) leads to theup-regulation of CYP7A1, the enzyme that catalyzes the rate limitingstep in the conversion of cholesterol to bile acids. In turn, bile acidssuch as chenodeoxycholic acid (CDCA, 1, a low affinity endogenousagonist for FXR, whose structure is shown below) are potent ligands forFXR, whose activation leads to down-regulation of CYP7A1, leading to thecompletion of the feedback circuit.

In this circuit FXR induces the expression of a transcriptionalrepressor SHP (small heterodimer partner) which in turn binds to LRH-1(liver receptor homolog), which is required in CYP7A activation.Additionally, both LXR and FXR are implicated in the regulation ofseveral other gene products involved in cholesterol absorption,metabolism and transport.

Thus, the identification of potent, selective, small molecule FXRagonists, partial agonists and antagonists would be powerful tools andwould have many potential applications. For example, such compoundswould facilitate the in vivo analysis of FXR physiology in vivo. Inaddition, such compounds, in conjunction with DNA arraying technology,might allow for the discovery of new gene products under the control ofFXR. Further, FXR modulators might find potential utility in thetreatment of cholestasis and other disease states associated withaberrant levels, flow and release of bile acids. Moreover, in theabsence of a crystal structure of FXR, a thorough structure-activityrelationship (SAR) study of ligands that modulate the activity of FXRwould allow for the delineation of the structural requirements forligand binding and might aid in the design of future ligands andpotential therapeutics.

SUMMARY OF THE INVENTION

In accordance with the present invention, the identification of novelpotent FXR activators is described. Initial screening of a10,000-membered, diversity-orientated library of benzopyran containingsmall molecules for FXR activation utilizing a cell-based reporter assayled to the identification of several lead compounds owning lowmicromolar activity (EC₅₀'s=5-10 μM. These compounds were systematicallymodified employing parallel solution-phase synthesis and solid-phasesynthesis to provide numerous compounds that potently activate FXR. Twoderivatives of invention compounds, bearing stilbene or biaryl moieties,contain members that are the most potent FXR agonists reported to datein cell-based assays. These compounds are useful as chemical tools tofurther define the physiological role of FXR as well as therapeuticleads for the treatment of diseases linked to cholesterol, bile acidsand their metabolism and homeostasis.

BRIEF DESCRIPTION OF THE FIGURE

FIG. 1 summarizes the efficacy of the functional assay for theidentification of FXR agonists, using the known FXR agonist,chenodeoxycholic acid (CDCA).

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, there are provided compoundshaving the structure:

wherein:

A is a C3 up to C8 branched chain alkyl or substituted alkyl group, a C3up to C7 cycloalkyl or substituted cycloalkyl, an optionally substitutedaryl or an optionally substituted heteroaryl,

X is —C(O)— or —CH₂—,

R is methyl or ethyl,

R¹ is H, hydroxy, alkoxy, benzoyloxy, mesityloxy, or —OCH₂C(O)OC₂H₅,

R² is H or R² can cooperate with R³ to form a benzopyran, wherein thepyran ring has the structure:

wherein:

-   -   R⁶ is not present if the pyran ring is unsaturated, or, if        present, is selected from H, —OR, wherein R is alkyl or acyl, or        R⁶ can cooperate with R⁷ to form a cyclic acetal, a cyclic        ketal, or a cyclopropyl moiety, and    -   only one of R⁷ and R⁸ is present if the pyran ring is        unsaturated, or R⁷ and R⁸ are independently H, carboxyl, cyano,        hydroxy, alkoxy, thioalkyl, aryl, or R⁷ and R⁸ taken together        comprise a carbonyl oxygen or an oxime nitrogen, or either R⁷ or        R⁸ can cooperate with R⁶ to form a cyclic acetal, a cyclic        ketal, or a cyclopropyl moiety,

R³ can cooperate with R² to form a benzopyran having the structure setforth above, or R³ is alkenyl, optionally substituted aryl orheteroaryl, or optionally substituted arylalkenyl or heteroarylalkenyl,

R⁴ is H or hydroxy, and

R⁵ is H, hydroxy, alkoxy or aryloxy.

As employed herein, “alkyl” refers to saturated straight or branchedchain hydrocarbon radical having in the range of 1 up to about 20 carbonatoms. “Lower alkyl” refers to alkyl groups having in the range of 1 upto about 5 carbon atoms. “Substituted alkyl” refers to alkyl groupsfurther bearing one or more substituents selected from hydroxy, alkoxy(of a lower alkyl group), mercapto (of a lower alkyl group), cycloalkyl,substituted cycloalkyl, heterocyclic, substituted heterocyclic, aryl,substituted aryl, heteroaryl, substituted heteroaryl, aryloxy,substituted aryloxy, halogen, trifluoromethyl, cyano, nitro, nitrone,amino, amido, —C(O)H, acyl, oxyacyl, carboxyl, carbamate,dithiocarbamoyl, sulfonyl, sulfonamide, sulfuryl, and the like.

As employed herein, “alkenyl” refers to straight or branched chainhydrocarbyl groups having at least one carbon-carbon double bond, andhaving in the range of about 2 up to 20 carbon atoms, and “substitutedalkenyl” refers to alkenyl groups further bearing one or moresubstituents as set forth above.

As employed herein, “alkoxy” refers to —O-alkyl groups having in therange of 2 up to 20 carbon atoms and “substituted alkoxy” refers toalkoxy groups further bearing one or more substituents as set forthabove.

As employed herein, “cycloalkyl” refers to a cyclic ring-containinggroups containing in the range of about 3 up to about 8 carbon atoms,and “substituted cycloalkyl” refers to cycloalkyl groups further bearingone or more substituents as set forth above.

As employed herein, “heterocyclic” refers to cyclic (i.e.,ring-containing) groups containing one or more heteroatoms (e.g., N, O,S, or the like) as part of the ring structure, and having in the rangeof 3 up to 14 carbon atoms and “substituted heterocyclic” refers toheterocyclic groups further bearing one or more substituents as setforth above.

As employed herein, “aryl” refers to aromatic groups having in the rangeof 6 up to 14 carbon atoms and “substituted aryl” refers to aryl groupsfurther bearing one or more substituents as set forth above.

As employed herein, “aryloxy” refers to —O-aryl groups having in therange of 6 up to 14 carbon atoms and “substituted aryloxy” refers toaryloxy groups further bearing one or more substituents as set forthabove.

As employed herein, “arylalkenyl” refers to aryl-substituted alkenylgroups and “substituted arylalkenyl” refers to arylalkenyl groupsfurther bearing one or more substituents as set forth above.

As employed herein, “heteroaryl” refers to aromatic groups having in therange of 4 up to about 13 carbon atoms, and at least one heteroatomselected from O, N, S, or the like; and “substituted heteroaryl” refersto heteroaryl groups further bearing one or more substituents as setforth above.

As employed herein, “heteroarylalkenyl” refers to heteroaryl-substitutedalkenyl groups and “substituted heteroarylalkenyl” refers toheteroarylalkenyl groups further bearing one or more substituents as setforth above.

As employed herein, “acyl” refers to alkyl-carbonyl species.

As employed herein, “halogen” refers to fluoride, chloride, bromide oriodide atoms.

As employed herein, reference to “a carbamate group” embracessubstituents of the structure —C(O)—NR₂, wherein each R is independentlyH, alkyl, substituted alkyl, aryl or substituted aryl as set forthabove.

As employed herein, reference to “a dithiocarbamate group” embracessubstituents of the structure —S—C(S)—NR₂, wherein each R isindependently H, alkyl, substituted alkyl, aryl or substituted aryl asset forth above.

As employed herein, reference to “a sulfonamide group” embracessubstituents of the structure —S(O)₂—NH₂.

As employed herein, “sulfuryl” refers to substituents of the structure═S(O)₂.

As employed herein, “amino” refers to the substituent —NH₂.

As employed herein, “monoalkylamino” refers to a substituent of thestructure —NHR, wherein R is alkyl or substituted alkyl as set forthabove.

As employed herein, “dialkylamino” refers to a substituent of thestructure —NR₂, wherein each R is independently alkyl or substitutedalkyl as set forth above.

As employed herein, reference to “an amide group” embraces substituentsof the structure —C(O)—NR₂, wherein each R is independently H, alkyl,substituted alkyl, aryl or substituted aryl as set forth above. Wheneach R is H, the substituent is also referred to as “carbamoyl” (i.e., asubstituent having the structure —C(O)—NH₂). When only one of the Rgroups is H, the substituent is also referred to as “monoalkylcarbamoyl”(i.e., a substituent having the structure —C(O)—NHR, wherein R is alkylor substituted alkyl as set forth above) or “arylcarbamoyl” (i.e., asubstituent having the structure —C(O)—NH(aryl), wherein aryl is asdefined above, including substituted aryl). When neither of the R groupsare H, the substituent is also referred to as “di-alkylcarbamoyl” (i.e.,a substituent having the structure —C(O)—NR₂, wherein each R isindependently alkyl or substituted alkyl as set forth above).

In accordance with a particular embodiment of the present invention,presently preferred compounds are those wherein A is a C5-C7 cycloalkylgroup.

In accordance with another particular embodiment of the presentinvention, presently preferred compounds are those wherein X is —C(O)—.

In accordance with yet another particular embodiment of the presentinvention, presently preferred compounds are those wherein R¹ ishydrogen.

In accordance with still another particular embodiment of the presentinvention, presently preferred compounds are those wherein R² and R³cooperate to form a benzopyran.

In accordance with a further particular embodiment of the presentinvention, presently preferred compounds are those wherein R³ isalkenyl, thereby producing a cinnamate derivative.

In accordance with a still further embodiment of the present invention,presently preferred compounds are those wherein R³ is an optionallysubstituted aryl or heteroaryl moiety, thereby producing biphenylderivatives.

In accordance with yet another embodiment of the present invention,presently preferred compounds are those wherein R³ is an optionallysubstituted arylalkenyl or heteroarylalkenyl moiety, thereby producingstilbene derivatives.

As there was, prior to the present invention, only one example of a highaffinity, non-steroidal agonist for FXR, i.e., GW 4064 (3, having anEC₅₀=80 nM, structure shown below), the strategy adopted herein foridentification of additional potent compounds involved screening a10,000-membered library constructed around the privileged2,2-dimethylbenzopyran scaffold.

Such privileged structures are attractive starting points for leadcompound discovery, particularly when there exists little structuralinformation regarding the target, as they show good binding affinitytoward a wide variety of enzymes and receptors. The initial hitsdiscovered from screening of this library for FXR activation could befurther modified for enhanced potency and pharmacological propertiessuitable for the applications mentioned above. Implementation of such astrategy is described herein, culminating in the discovery of numerouspotent and selective activators of FXR.

Thus, in accordance with the present invention, a cell-basedtranscription assay is employed in which an FXR responsive promoter islinked to a luciferase reporter as the primary screen (see Example 1).In addition to ensuring that only cell permeable compounds were selectedfor further optimization, this approach allows for the detection of FXRactivation in a natural system (i.e., correct folding of the protein andin the presence of a complete compliment of co-activators andco-repressors). Initial screening of a 10,000-membered combinatoriallibrary of benzopyran-based small molecules in this high-throughput,cell-based assay for FXR activation produced several lead compounds,4-15, whose structures are shown below:

Guided by the preliminary structure-activity relationships (SAR) gainedfrom the evaluation of this initial library, a follow-up focused libraryof about 200 benzopyran-based compounds was designed and synthesized onsolid support employing the protocol set forth below.

A selection of the most active compounds, possessing activities from5-10 μM, discovered from this second round of screening, includescompounds 16-27, as shown below:

Compounds 26 and 27 proved to be among the most active at this stage andwere the subject of further modification as described below.

With initial lead compounds identified and validated, the stage is setfor the systematic modification of the three regions of lead compound26, as shown below:

As detailed in the following sections, focused libraries weresynthesized and screened in the cell-based assay in order to evaluatethe structural requirements of each region of the molecule for potentFXR agonism. At this point parallel solution-phase chemistry wasselected for the construction of additional focused libraries. Thisshift away from solid-phase chemistry provided maximum flexibility inefforts to rapidly and systematically modify each region of the leadmolecules using smaller designed libraries.

Most of the FXR agonists reported to date, including CDCA (1; seestructure above), TTNPB (2; structure shown below) and GW4064 (3; seestructure above), contain a carboxylic acid moiety.

It was reasoned, therefore, that incorporation of an acid unit withineither region I, II or III of lead compound 26 (as illustrated above)would confer increased potency upon this rather weak ligand (5-10 μM)identified via HTS.Evaluation of the Benzopyran Region I SAR

Guided by this reasoning, the SAR of region I was evaluated. Severalcompounds displaying the acid unit in various positions (e.g., Compounds28, 36, 52, 54 and 56), were prepared (see, Examples 3 to 6) and tested.

None of these compounds, however, showed improved activation of FXR.Interestingly, compound 29, bearing a meta methyl acrylate moiety, was asubstantially better activator of FXR than compound 26.

In further refining the SAR of region I, it was observed that thelocation of the methyl acrylate moiety at the meta position wasbeneficial to achieve potent activation of FXR, as compound 53, bearinga para methyl acrylate, does not activate FXR under the conditionstested. In order to further examine what functionality was tolerable atthe meta position, additional compounds with meta substituents (as shownabove) were synthesized. From biological screening of these compounds itbecame clear that the length and rigidity of the tether between thearomatic core and the interacting functionality (either methyl ester ormethyl ether) are important for FXR agonism. For instance, compounds 41and 45 appear to possess either too short or too long of a tether forpotent, activity; compounds 35 and 46-49 presumably cannot adopt thecorrect orientation for potent activation; and compounds 30, 31, 34, 38,39, 40 and 50 do not apparently present the correct interactingfunctionality to the receptor as they are inactive. Indeed, of all theanalogs designed to probe the SAR of region I, only compounds 29 and 33are capable of activating FXR to a significant extent. Due to relativeease of synthesis of compound 29 this analog was chosen as a startingpoint for the modification of region II.

Evaluation of the Benzopyran Region II SAR

Benzopyran region II SAR was evaluated through traditional solutionphase chemistry to see the effect of various substitution patterns inthis region of the molecule. Thus, compounds 61-84 (structures shownbelow) were prepared (see, Example 7) and tested.

Only compounds 65 (EC₅₀=358 nM) and 68 (EC₅₀=1,000 nM) were moreeffective than compound 29 in activating FXR. Substituted aromatic amidederivatives such as 69-77 were all found to be less active than theparent compound 68. Alkyl derivatives 78 and 79 were inactive as weresulfonamide 82, thiourea 84, and thioamide 83, suggesting the importanceof acylation at this position. The sum of these results pointed to thedesirable presence of moderately bulky cycloalkyl amide moieties inregion II for good activity.

Evaluation of the Benzopyran Region III SAR

Having thoroughly examined regions I and II, the modification of regionIII was then undertaken. Thus, compounds 85-102 (structures shown below,along with compound 68 for ease of comparison) were prepared (seeExamples 8 and 9) and tested.

Incorporation of polar H-bond donating functional groups such as thosethat adorn compounds 86, 93, 94, 98 and 100 did not improve the activityof the analogs. Nor did the addition of H-bond acceptors such as in 89,90, 95, 99 and 101 improve the ability of the parent compound 68 toactivate FXR.

The addition of bulky lipophilic groups to the benzopyran moietyafforded compounds that only weakly activated FXR. However, replacementof the double bond in the benzopyran unit by a dichlorocyclopropane unitprovided analog 102 (EC₅₀=333 nM). Replacement of the benzoyl group inregion II of compound 102 with the cyclohexylcarbonyl moiety affordedthe even more potent compound 149 (EC₅₀=188 nM).

Although compound 149 (EC₅₀=188 nM) represents a significant improvementin potency over compound 65 (EC₅₀=348 nM), it was not readily apparenthow the activity of this class of compounds could be further improved.Therefore, it was decided to examine the effect of replacing thebenzopyran moiety with other ring systems.

Thus, a series of compounds (i.e., Compounds 104-129) in which thebenzopyran moiety was replaced with certain groups of varying moleculardiversity was prepared (see Examples 10 to 17) and tested.

Biological assays showed that replacement of the benzopyran with a smallaromatic unit generally had a detrimental effect on activity. Forinstance, compounds 110 and 112-117 were inactive, while compounds 111and 118 showed only moderate activation of FXR (EC₅₀=680 nM and 606 nM,respectively; see Table 3 in Example 1). However, replacement of thebenzopyran with an aromatic ring bearing substituents at the paraposition produced compounds with improved activity. For example,4-tert-butyl cinnamate 105 (EC₅₀=127 nM), stilbenes 121 and 122 (EC₅₀=36and 208 nM, respectively), biaryls 124-127 (EC₅₀=510, 69, 77, 227 nM,respectively) and aryl thiophenes 128 and 129 (EC₅₀=206 and 256 nM,respectively) were all potent activators of FXR in the cell-basedreporter assay (see Tables 1, 9, 10 and 11 in Example 1).

This initial survey of the three regions of SAR outlined above led tothe identification of several potent FXR agonists for furtherevaluation. One such agonist is the benzopyran-deriveddichlorocyclopropane 149 (EC₅₀=188 nM). Compound 105 (EC₅₀=127 nM) is anexample of a bis-cinnamate derivative. Finally, compounds 121 (EC₅₀=36nM) and 124 (EC₅₀=69 nM) are stilbene and biaryl derivatives,respectively, of invention compounds.

Based on the results observed thus far, compound 149 appeared torepresent the most potent derivative that could be readily obtainedamong the benzopyran-derivatives. However, the bis-cinnamate, biaryl,and stilbene derivatives of invention compounds were thought to stillpossess considerable potential for further development and rigorous SARanalysis. Below the results of such investigations are detailed, whichindeed led to further enhancement of biological activity.

Examination of the Bis-Cinnamate Series

Similar to the results described above, the meta substituted methylcinnamate moiety on the “right-hand” region of the molecule remained adesirable component for elevated activity among the bis-cinnamatederivatives of invention compounds (see compounds 105 and 133-139).

Replacement of the methyl acrylate unit with either a methyl or ethylallylic ether (compounds 136 and 137) caused only a slight decrease inactivity (EC₅₀=243 and 220 nM, respectively). A marked decline inpotency accompanied substitution of the methyl acrylate by moresterically bulky ethers or esters (compounds 133 and 134) or amides(compound 135). Interestingly, saturation of the acrylate olefin(compound 139) afforded only a two-fold decrease in potency, EC₅₀=274nM, which supports the notion that conformational rigidity is a factorcontributing to, but not essential for, high affinity ligands.Importantly, compound 139 suggests that the methyl acrylate moiety isnot simply functioning as a latent electrophile.

Region II also closely mirrored the preceding data as cycloalkyl amidesremained the preferred substituents (see, compounds 105 and 140-145:EC₅₀=127-250 nM) among the bis-cinnamate derivatives of inventioncompounds. Aromatic and heterocyclic amides as well as alkyl ureas ledto moderate potency (compounds 143-145: EC₅₀=205-236 nM) whereasincorporation of bulky ureas such as compound 146 rendered compounds ofonly marginal efficacy.

As mentioned above, replacement of the benzopyran moiety with a benzylgroup bearing a tert-butyl acrylate moiety in the para-position yieldedcompound 105 with dramatically increased efficacy (EC₅₀=127 nM).Interestingly, placement of the same tert-butyl acrylate group in eitherthe meta or ortho positions of the aromatic ring in Region III led toonly micromolar potency (see compounds 107 and 109). Furtherinvestigation of the “left-hand” region in this series of compoundsdemonstrated that a decrease in ester group size yielded a correspondingdecrease in efficacy (EC₅₀ of t-butyl>i-propyl>ethyl>methyl (see,compounds 105 and 150-152). Similarly, substitution of the ester witheither carboxylic acid or amide functionality provided less effectivecompounds with EC₅₀ values in the micromolar range. Substitution of thetert-butyl acrylate moiety with a methyl or ethyl allylic ether (see,compounds 156 and 157) retained considerable potency (EC₅₀=233 and 198nM, respectively). However, the more bulky phenyl allylic ether 158possessed only micromolar activity. In addition, saturation of theacrylate moiety (compound 159) showed a two-fold decrease in potencyfrom the parent compound 105. Finally, substitution of the orthoposition of the aromatic ring of the tert-butyl acrylate series withoxygenated functionality afforded compounds with very low biologicalactivity (see compounds 161-167).

Construction of Biaryl and Stilbene Containing Focused Libraries

In an effort to further explore the activities of biaryl and stilbenederivatives of invention compounds, a 94-membered library of suchcompounds was constructed employing a solid phase strategy (see Example18).

The selection of appropriate styrenes and boronic acids for inputs intothis combinatorial library was guided by initial comparisons oftert-butyl stilbene (compound 123, EC₅₀=>1000 nM) to the unsubstitutedstilbene 102 (EC₅₀=36 nM), and biaryl compound 124 (EC₅₀=510 nM) tocompound 125 (EC₅₀=69 nM). It was reasoned that both the stilbene andthe biaryl ligands needed to fit into the same region of space withinthe receptor site for potent activation. Thus, stilbenes in which thearomatic nucleus is removed two carbon atoms further away from the coreof the molecule should be adorned with small substituents while thebiaryl compounds should be adorned with larger functionality for optimalactivity. Screening of this compound library in the cell-based assay ledto some intriguing results as summarized in Tables 12-15 of Example 1.

Thus, it was found that in both stilbene and biaryl derivatives ofinvention compounds, analogs bearing the cyclohexylamide moiety aregenerally the most potent followed by those bearing the isopropyl amideor isopropyl urea units. As predicted above, stilbenes bearing smallersubstituents were more potent than those bearing larger functionality.For instance, substituted stilbene 121 and mono-fluoro stilbenes 192,201, and 204 were among the most active, while mono-methyl derivative174 and tri-methyl derivative 195 were among the least active. Also ofinterest were heterocyclic compounds 207 and 210, which retained goodpotency (EC₅₀=309 and 227 nM, respectively) and may possess improvedpharmacological properties. With biaryl derivatives of inventioncompounds, compounds which present more bulk at the terminus of thestructure were more active. With these derivatives, compounds 259(EC₅₀=25 nM) and 244 (EC₅₀=38 nM) were particularly active. Overall,most of the compounds synthesized in this follow-up library wereefficient activators of FXR, confirming the accuracy of the workinghypothesis for the FXR binding pocket described above, which provides asolid basis for further development of FXR activators.

A summary of the molecular requirements for potent FXR activation isshown below:

Thus, in Region I the presence of the meta methyl acrylate unit orallylic methyl ether is desirable for potent activation as only a fewmodifications retain good activity. In some instances, when other areasare modified, the olefin can be deleted from Region I while retainingpotency. The most potent compounds observed thus far possess an amide ora urea in Region II. Presently most preferred compounds have acycloalkylamide or a cycloalkylurea in Region II. Finally, Region III isthe most tolerant, indeed, several structural elements were found toprovide a good fit within the pocket of the receptor. Generally, it isdesirable for the aromatic ring to be para-substituted, with the stericbulk and length of the substituent imparting a significant effect onpotency of the resulting compound.

In order to determine how selectively the above-described compoundsactivated FXR, some of the most active compounds were screened against apanel of nuclear receptors. Most of these compounds were found to beselective for activation only of FXR. Notably, however, compound 149also potently activated SXR. This result may lead to compounds whichhave utility in the treatment of diseases linked to the accumulation oftoxic bile acids.

In accordance with another embodiment of the present invention, thereare provided formulations comprising at least one of the above-describedcompounds in a pharmaceutically acceptable carrier therefor. Exemplarypharmaceutically acceptable carriers include solids, solutions,emulsions, dispersions, micelles, liposomes, and the like. Optionally,the pharmaceutically acceptable carrier employed herein furthercomprises an enteric coating.

Pharmaceutically acceptable carriers contemplated for use in thepractice of the present invention are those which render inventioncompounds amenable to oral delivery, transdermal delivery, intravenousdelivery, intramuscular delivery, topical delivery, nasal delivery, andthe like.

Thus, formulations of the present invention can be used in the form of asolid, a solution, an emulsion, a dispersion, a micelle, a liposome, andthe like, wherein the resulting formulation contains one or more of thecompounds of the present invention, as an active ingredient, inadmixture with an organic or inorganic carrier or excipient suitable forenterable or parenteral applications. The active ingredient may becompounded, for example, with the usual non-toxic, pharmaceuticallyacceptable carriers for tablets, pellets, capsules, suppositories,solutions, emulsions, suspensions and any other suitable for use. Thecarriers which can be used include glucose, lactose, gum acacia,gelatin, manitol, starch paste, magnesium trisilicate, talc, cornstarch, keratin, colloidal silica, potato starch, urea, medium chainlength triglycerides, dextrans, and other carriers suitable for use inmanufacturing preparations, in solid, semisolid, or liquid form. Inaddition auxiliary, stabilizing, thickening, and coloring agents andperfumes may be used. The active compound(s) is (are) included in theformulation in an amount sufficient to produce the desired effect uponthe process or disease condition.

Invention formulations containing the active ingredient may be in a formsuitable for oral use, for example, as tablets, troches, lozenges,aqueous or oily suspensions, dispersible powders or granules, emulsions,hard or soft capsules, or syrups or elixirs. Formulations intended fororal use may be prepared according to any method known to the art forthe manufacture of pharmaceutical compositions and such formulations maycontain one or more agents selected from the group consisting of asweetening agent such as sucrose, lactose, or saccharin, flavoringagents such as peppermint, oil of wintergreen or cherry, coloring agentsand preserving agents in order to provide pharmaceutically elegant andpalatable preparations. Tablets containing the active ingredient inadmixture with non-toxic pharmaceutically acceptable excipients used maybe, for example (1) inert diluents such as calcium carbonate, lactose,calcium phosphate or sodium phosphate; (2) granulating anddisintegrating agents such corn starch, potato starch or alginic acid;(3) binding agents such as gum tragacanth, corn starch, gelatin oracacia, and (4) lubricating agents such as magnesium stearate, stericacid or talc. The tablets may be uncoated or they may be coated by knowntechniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a sustained action over alonger period. For example, a time delay material such as glycerylmonostearate or glyceryl distearate may be employed. They may also becoated by such techniques as those described in U.S. Pat. Nos.4,256,108; 4,160,452; and 4,265,874, to form osmotic therapeutic tabletsfor controlled release.

In some cases, formulations contemplated for oral use may be in the formof hard gelatin capsules wherein the active ingredient is mixed withinert solid diluent(s), for example, calcium carbonate, calciumphosphate or kaolin. They may also be in the form of soft gelatincapsules wherein the active ingredient is mixed with water or an oilmedium, for example, peanut oil, liquid paraffin, or olive oil.

Invention formulations may be in the form of a sterile injectablesuspension. This suspension may be formulated according to known methodsusing suitable dispersing or wetting agents and suspending agents. Thesterile injectable preparation may also be a sterile injectable solutionor suspension in a non-toxic parenterally-acceptable diluent or solvent,for example, as a solution in 1,3-butanediol. Sterile, fixed oils areconventionally employed as a solvent or suspending medium. For thispurpose any bland fixed oil may be employed including synthetic mono- ordiglycerides, fatty acids, naturally occurring vegetable oils likesesame oil, coconut oil, peanut oil, cottonseed oil, etc. or syntheticfatty vehicles like ethyl oleate or the like. Buffers, preservatives,antioxidants, and the like can be incorporated as required.

Invention formulations may also be administered in the form ofsuppositories for rectal administration of the drug. These formulationsmay be prepared by mixing the drug with a suitable non-irritatingexcipient, such as cocoa butter, synthetic glyceride esters ofpolyethylene glycols, which are solid at ordinary temperatures, butliquefy and/or dissolve in the rectal cavity to release the drug. Sinceindividual subjects may present a wide variation in severity of symptomsand each drug has its unique therapeutic characteristics, the precisemode of administration and dosage employed for each subject is left tothe discretion of the practitioner.

Amounts effective for the particular therapeutic goal sought will, ofcourse, depend on the severity of the condition being treated, and theweight and general state of the subject. Various general considerationstaken into account in determining the “effective amount” are known tothose of skill in the art and are described, e.g., in Gilman et al.,eds., Goodman And Gilman's: The Pharmacological Bases of Therapeutics,8th ed., Pergamon Press, 1990; and Remington's Pharmaceutical Sciences,17th ed., Mack Publishing Co., Easton, Pa., 1990, each of which isherein incorporated by reference.

The term “effective amount” as applied to invention compounds, means thequantity necessary to effect the desired therapeutic result, forexample, a level effective to treat, cure, or alleviate the symptoms ofa disease state for which the therapeutic compound is beingadministered, or to establish homeostasis. Since individual subjects maypresent a wide variation in severity of symptoms and each drug or activeagent has its unique therapeutic characteristics, the precise mode ofadministration, dosage employed and treatment protocol for each subjectis left to the discretion of the practitioner.

In accordance with yet another embodiment of the present invention,there are provided methods for modulating process(es) mediated byfarnesoid X receptor polypeptides, said methods comprising conductingsaid process(es) in the presence of an effective amount of at least onecompound according to the invention.

As employed herein, “modulating” refers to the ability of a modulatorfor a member of the nuclear receptor superfamily (e.g., FXR) to eitherdirectly (by binding to the receptor as a ligand) or indirectly (as aprecursor for a ligand or an inducer which promotes production of ligandfrom a precursor) induce expression of gene(s) maintained under hormoneexpression control, or to repress expression of gene(s) maintained undersuch control. Exemplary processes contemplated for modulation accordingto the invention include cholesterol metabolism, regulation of lipidhomeostasis, stimulation of bile transport and absorption, regulation ofthe expression of genes involved in the excretion and transportation ofbile acids (including intestinal bile acid-binding protein (IBABP)),bile salt export pump (BSEP) and canalicular multi-specific organicanion transporter (cMOAT), and the like.

Bile acids are derivatives of cholesterol synthesized in the hepatocyte.Cholesterol, ingested as part of the diet or derived from hepaticsynthesis is converted into the bile acids cholic and chenodeoxycholicacids, which are then conjugated to an amino acid (glycine or taurine)to yield the conjugated form that is actively secreted into cannaliculi.Bile acids are facial amphipathic, that is, they contain bothhydrophobic (lipid soluble) and polar (hydrophilic) faces. Thecholesterol-derived portion of a bile acid has one face that ishydrophobic (that with methyl groups) and one that is hydrophilic (thatwith the hydroxyl groups); the amino acid conjugate is polar andhydrophilic. Therefore, compounds that can be used to modulate suchpathways via effects on FXR involving bile acids are useful incholesterol metabolism.

Bile acid synthesis is a major pathway for cholesterol disposal and thusrepresents a potential therapeutic target pathway for the treatment ofhypercholesterolemia. FXR acts as a bile acid receptor and biologicalsensor for the regulation of bile acid biosynthesis. FXR is known toregulate cholesterol metabolism in two ways: (1) chenodeoxycholic acid(CDCA), a primary bile acid, binds directly to and activates FXR, whichthen mediates the feedback suppression by bile acids of cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acidbiosynthesis from cholesterol; and (2) FXR participates in theactivation of intestinal bile acid binding protein (IBABP), which isinvolved in the enterohepatic circulation of bile acids. Thus FXRconstitutes a potential therapeutic target that can be modulated toenhance the removal of cholesterol from the body. Novel compoundsidentified by the methods presented herein provide a new tool forregulating or modulating FXR function.

Furthermore, FXR is known to in turn activate a series of target genes.In particular FXR functions as a heterodimer with the 9-cis-retinoicacid receptor (RXR). A number of target DNA binding sequences that wouldbe present in target genes have recently been identified. A consensussequence has been determined, which contains an inverted repeat of thesequence AGGTCA with a 1-base pair spacing (IR-1) (Laffitte et al., J.Biol. Chem. 275:10638-10647 (2000). This sequence was shown to be a highaffinity binding site for FXR/RXR in vitro and to conferligand-dependent transcriptional activation by FXR/RXR to a heterologouspromoter in response to a bile acid or synthetic retinoid. Althoughthese studies demonstrated that the FXR/RXR heterodimer binds to theconsensus IR-1 sequence with the highest affinity, it was alsodemonstrated that FXR/RXR can bind to and activate through a variety ofelements including IR-1 elements with changes in the core half-sitesequence, spacing nucleotide, and flanking nucleotides. In addition, itwas shown that FXR/RXR can bind to and transactivate through directrepeats. Therefore, by providing novel ways to modulate FXR function,the present invention in turn provides a method of modulating thefunction of a variety of target genes that are acted upon by FXR.

In accordance with still another embodiment of the present invention,there are provided methods for the treatment of hypercholestemia, saidmethods comprising administering an effective amount of at least onecompound according to the invention to a subject in need thereof.

In accordance with still another embodiment of the present invention,there are provided methods for the treatment of cholestasis, saidmethods comprising administering an effective amount of at least onecompound according to the invention to a subject in need thereof.

The invention will now be described in greater detail with reference tothe following non-limiting Examples.

Example 1 In Vivo Assay

The feasibility of creating high throughput screens (HTS) for ORs wasexplored using FXR as a candidate orphan receptor (OR) with a knownactivator, chenodeoxycholic acid (CDCA) as a ligand. The screen is basedon the co-transfection of a full-length receptor with the reportervector containing a natural hormone response element under a minimaleukaryotic promoter. The results provided herein (see, FIG. 1)demonstrate that compounds can be successfully screened in a dosedependent manner for potential activating chemical ligands using a fulllength FXR on a natural response element. These results validate therobustness of the assay for FXR, in 384-well plates. Using this 384-wellformat, the high throughput screening (HTS) approach to FXR as acandidate OR was employed. For this test screen, a 10,000 memberedlibrary, constructed around the privileged 2,2-dimethylbenzopyranscaffold, was employed (see Nicolaou et al., J. Am. Chem. Soc.122:9939-9953 and 9954-9967 (2000)). This library comprisesapproximately 10,000 distinct compounds with structures and sizessimilar to natural products such as phyto-estrogens, flavanoids,coumarins and long chain fatty acids. A central question in thefeasibility studies is whether this library is suitable for screeningfor nuclear receptor ligands. Samples of this library were firstreformatted into a 384-well format and then subjected to the FXRcell-based assays described above and assessed for FXR-mediatedtranscriptional activity. Cells were exposed to approximately 10 μM ofsample for 18 hrs prior to washing and luciferase analysis.

The 25 most active compounds at 10 μM were re-synthesized to confirmtheir structure and activity. Smaller “focused” chemical libraries werethen designed and prepared around these hits and subjected to multiplerounds of screening. Through this iterative process a total of sevenadditional rounds of synthesis and selection was conducted resulting innovel compounds that are as effective as a proprietary synthetic liganddeveloped by Glaxo-Smith-Kline (GW 4064) in cell based assays. Using oneof these identified compounds, fexaramate (105; EC₅₀ 127 nM), as ascaffold, three additional focused libraries were made and screened toobtain at least four potent, non-steroidal FXR agonists termed fexarene(121; EC₅₀, 36 nM), fexaramine (259; EC₅₀, 25 nM), fexarine (244; EC₅₀,38 nM) and fexarchloramide (149; EC₅₀, 188 nM). EC₅₀ values weredetermined with Prism 3.0 software via the activity of the subjectcompound in the previously described cell based assay.

EC₅₀ values for the “scaffold” compound, fexaramate (105), and numerousvariations thereof, are presented below (see Tables 1-11).

TABLE 1

a. SAR of region I R EC₅₀ (nM) RE^(a) 105 COOMe 127 2.12 133 COOEt 2562.07 134 COO^(t)Bu >1000 1.06 135 CONH₂ >1000 0.50 136 CH₂OMe 243 1.68137 CH₂OEt 220 1.74 138 CH₂OPh 2830 0.45

139: EC₅₀ = 274 nM RE^(a) = 1.38

TABLE 2

b. SAR of region II R EC₅₀ (nM) RE^(a) 140 cyclopropyl 250 1.68 141cyclobutyl 187 1.84 142 cyclopentyl 162 2.16 105 cyclohexyl 127 2.12 143phenyl 238 1.96 144 2-furyl 205 1.93 145 isopropylamino 212 1.96 146benzylamino >1000 0.27

TABLE 3

c. SAR of region III R EC₅₀ (nM) RE^(a) 132 H >1000 0.09 147methyl >1000 0.09 110 benzyl >1000 0.09 111 2-napthyl 880 0.41 1142-bromobenzyl >1000 0.11 113 3-bromobenzyl >1000 0.11 1124-bromobenzyl >1000 0.28 148 4-tert-butylbenzyl >1000 0.15 1153-mathoxybenzyl >1000 0.11 118 3,5-dimethoxybenzyl 606 0.11 1173-(trifluoromethyl)benzyl >1000 0.12

TABLE 4

R EC₅₀ (nM) RE^(a) 68 phenyl >1000 0.83 65 cyclohexyl 3.58 0.40

TABLE 5

R EC₅₀ (nM) RE^(a) 102 phenyl 333 0.64 149 cyclohexyl 188 0.50

TABLE 6

d. SAR of region III R EC₅₀ (nM) RE^(a) 104 COOH >1000 0.08 150COOMe >1000 0.87 151 COOEt >1000 1.14 152 COOPr 163 1.97 105 COO^(t)Bu127 2.12 153 COOBn >1000 0.23 154 CONMe₂ >1000 0.66 155 CONH^(t)Bu >10001.65 156 CH₂OMe 233 1.63 157 CH₂OEt 198 2.06 158 CH₂OPh >1000 0.64

TABLE 7

R EC₅₀ (nM) RE^(a) 159 COOMe 240 1.56 160 COO^(t)Bu >1000 0.64

TABLE 8

R EC₅₀ (nM) RE^(a) 161 H >1000 0.12 162 Me >1000 0.14 163 Bn >1000 0.38164 MeC(O) >1000 0.16 165 C₈H₅C(O) >1000 0.16 166 MeS(O₂) >1000 0.18 167EtOOCCH₂ >1000 0.18

TABLE 9

R¹ R² EC₅₀ (nM) RE^(a) ; OMe H 77 1.51 127 C(O)Me H 227 1.30 125 H SMe89 1.74 124 H H 510 0.71

TABLE 10

R EC₅₀ (nM) RE* 128 Me 206 1.78 129 C(O)Me 256 1.48

TABLE 11

R EC₅₀ (nM) RE^(a) 121 H 36 1.55 122 OMe 208 1.67 123 t-Bu >1000 0.29

Several of the derivatives set forth above are seen to possess excellentactivity (e.g., Compounds 121, 125, 141, 142, etc.).

EC₅₀ values for numerous additional variations of the compoundspresented above are presented below (see Tables 12-15).

TABLE 12

R¹ R² R³ R⁴ R⁵ R⁶ EC₅₀ (nM) RE^(a) 174 H H Me H H —C₈H₁₁ 342 0.83 175 HH Me H H —CH(CH₃)₂ 1410 0.37 176 H H Me H H —NHCH(CH₃)₂ 3570 0.10 177 ClH H H Cl —C₈H₁₁ 150 0.12 178 Cl H H H Cl —CH(CH₃)₂ 195 0.14 179 Cl H H HCl —NHCH(CH₃)₂ 216 0.15 180 H Cl H H H —C₆H₁₁ 165 1.41 181 H Cl H H H—CH(CH₃)₂ 164 1.09 182 H Cl H H H —NHCH(CH₃)₂ 339 0.59 183 H CF₃ H CF₃ H—C₈H₁₁ 1470 0.15 184 H CF₃ H CF₃ H —CH(CH₃)₂ 1950 0.13 185 H CF₃ H CF₃ H—NHCH(CH₃)₂ 1830 0.13 186 H CF₃ H H H —C₆H₁₁ 937 0.35 187 H CF₃ H H H—CH(CH₃)₂ 267 0.70 188 H CF₃ H H H —NHCH(CH₃)₂ 932 0.31 189 F H H H F—C₆H₁₁ 174 0.94 190 F H H H F —CH(CH₃)₂ 108 0.79 191 F H H H F—NHCH(CH₃)₂ 4020 0.21 192 F H H H H —C₆H₁₁ 64 1.41 193 F H H H H—CH(CH₃)₂ 70 1.17 194 F H H H H —NHCH(CH₃)₂ 431 0.69 195 Me H Me H Me—C₆H₁₁ 518 0.24 196 Me H Me H Me —CH(CH₃)₂ 149 0.30 197 Me H Me H Me—NHCH(CH₃)₂ 431 0.14 121 R H H H H —C₆H₁₁ 36 1.55 198 H H H H H—CH(CH₃)₂ 65 1.33 200 H H H H H —NHCH(CH₃)₂ 119 1.38 201 H F H H H—C₆H₁₁ 86 1.36 202 H F H H H —CH(CH₃)₂ 71 1.33 203 H F H H H —NHCH(CH₃)₂467 0.61 204 H H F H H —C₆H₁₁ 185 0.53 205 H H F H H —CH(CH₃)₂ 120 1.19206 H H F H H —NHCH(CH₃)₂ 348 0.91

TABLE 13

R EC₅₀ (nM) RE^(a) 207 —C₆H₁₁ 309 0.81 208 —CH(CH₃)₂ 310 0.62 209—NHCH(CH₃)₂ 575 0.68

TABLE 14

R EC₅₀ (nM) RE^(a) 210 —C₆H₁₁ 227 0.53 211 —CH(CH₃)₂ 228 0.32 212—NHCH(CH₃)₂ 368 0.42

TABLE 15

R¹ R² R³ R⁴ R⁵ R⁶ EC₅₀ (nM) RE^(a) 213 H F F H H —C₆H₁₁ 72 1.70 214 H FF H H —CH(CH₃)₂ 249 1.15 215 H F F H H —NHCH(CH₃)₂ 8180 0.23 125 H H SMeH H —C₆H₁₁ 69 1.74 216 H H SMe H H —CH(CH₃)₂ 51 0.98 217 H H SMe H H—NHCH(CH₃)₂ 178 0.23 218 OMe H H H H —C₆H₁₁ 359 0.49 219 OMe H H H H—CH(CH₃)₂ 377 0.28 220 OMe H H H H —NHCH(CH₃)₂ 4010 0.09 126 H Cl H Cl H—C₆H₁₁ 284 0.95 221 H Cl H Cl H —CH(CH₃)₂ 661 0.54 222 H Cl H Cl H—NHCH(CH₂)₂ <10000 0.10 223 H OMe H H H —C₆H₁₁ 101 1.51 224 H OMe H H H—CH(CH₃)₂ 72 1.28 225 H OMe H H H —NHCH(CH₃)₂ 1370 0.41 226 H OEt H H H—C₆H₁₁ 147 1.37 227 H OEt H H H —CH(CH₃)₂ 173 1.03 228 H OEt H H H—NHCH(CH₃)₂ 2350 0.33 229 H H OMe H H —C₆H₁₁ 89 1.71 230 H H OMe H H—CH(CH₃)₂ 97 1.21 231 H H OMe H H —NHCH(CH₃)₂ 144 1.18 232 H Cl H H H—C₆H₁₁ 94 1.56 233 H Cl H H H —CH(CH₃)₂ 77 1.52 234 H Cl H H H—NHCH(CH₃)₂ 1400 0.49 235 H H Me H H —C₆H₁₁ 26 1.38 236 H H Me H H—CH(CH₃)₂ 118 1.48 237 H H Me H H —NHCH(CH₃)₂ 449 0.80 238 H Me H H H—C₆H₁₁ 109 1.43 239 H Me H H H —CH(CH₃)₂ 163 1.09 240 H Me H H H—NHCH(CH₃)₂ 1330 0.53 241 OMe H H Cl H —C₆H₁₁ 233 1.16 242 OMe H H Cl H—CH(CH₃)₂ 226 0.79 243 OMe H H Cl H —NHCH(CH₃)₂ 3080 0.17 244 H —OCH₃O—H H —C₆H₁₁ 38 1.90 245 H —OCH₂O— H H CH(CH₃)₂ 19 1.25 246 H —OCH₂O— H H—NHCH(CH₃)₂ 96 1.51 247 H Cl F H H —C₆H₁₁ 66 1.87 248 H Cl F H H—CH(CH₃)₂ 129 1.64 249 H Cl F H H —NHCH(CH₃)₂ 3050 0.41 250 H H OCF₃ H H—C₆H₁₁ 264 1.04 251 H H OCF₃ H H —CH(CH₃)₂ 219 0.78 252 H H OCF₃ H H—NHCH(CH₃)₂ 7530 0.21 253 H OCF₃ H H H —C₆H₁₁ 420 0.84 254 H OCF₃ H H H—CH(CH₃)₂ 247 0.69 255 H OCF₃ H H H —NHCH(CH₃)₂ >10000 0.09 256 OMe H HH OMe —C₆H₁₁ 77 0.12 257 OMe H H H OMe —CH(CH₃)₂ 95 0.10 258 OMe H H HOMe —NHCH(CH₃)₂ 561 0.10 259 H H NMe₂ H H —C₆H₁₁ 25 1.72 260 H H NMe₂ HH —CH(CH₃)₂ 57 1.07 261 H H NMe₂ H H —NHCH(CH₃)₂ 162 1.01 262 H H t-Bu HH —C₆H₁₁ 132 1.38 263 H H t-Bu H H —CH(CH₃)₂ 343 0.59 264 H H t-Bu H H—NHCH(CH₃)₂ 262 1.02

Several of the derivatives set forth above are seen to possess excellentactivity (e.g., Compounds 177, 180, 181, 189, 190, 192, 193, 198, 201,202, 204, 205, 213, 216, 224, 229, 230, 232, 233, 235, 236, 238, 244,245, 246, 247, 256, 257, 259, 260, etc.).

Example 2 In Vitro Screening

An in vitro based “proximity” screen is an excellent complement to livecell assays and can be used as a measure of direct ligand binding. Hencethis type of screen is also an effective measure of the affinity ofbinding without the use of a radiolabel. The approach employed herein istermed AlphaScreen technology. For this assay purified receptor proteinis expressed as a glutathione S-transferase (GST) fusion protein and isbound via a GST antibody to a “donor” bead. This is then mixed with abiotinylated co-activator peptide that has been linked to an Avidinproximity sensitive “acceptor” bead. These reactants are mixed in a384-well plate and are then exposed to either a known inducer (control)or an ordered array of unknown compounds (library). If the acceptor bead(linked to the co-activator peptide) is brought into close proximity ofthe donor bead, by virtue of a biological interaction, singlet-stateoxygen molecules are released and react with chemiluminescent groups inthe acceptor beads. The effect of either known inducers or candidatechemical compounds on the interaction of a receptor and its co-activatorpeptide can be measured by a change in the Alpha signal.

The ability of the in vitro AlphaQuest assay to detectreceptor/co-activator peptide interactions in a 384 well format has beenevaluated using the thyroid hormone receptor (TR) and the retinoid Xreceptor (RXR) as positive controls. The results demonstrate thatreceptor/co-activator peptide interactions can be detected in adose-dependent manner with binding efficiencies similar to thosereported in the literature, validating this as a critical in vitroapproach to demonstrate binding of candidate ligands in the absence of ahigh affinity radiolabeled competitor.

Representative procedures for the preparation of Region I modifiedcompounds are shown in Examples 3 to 6.

Example 3 Preparation of Compounds 29, 60, S-5, S-6 and S-9

The strategy employed for the preparation of Compound 29 is shown below.

Thus, 2,3-dihydroxy benzaldehyde 59 is selectively methylated (NaH, MeI)to afford the monoalcohol benzaldehyde S-5. S-5 is O-alkylated (1.5equiv. of 2-methyl-3-butyn-2-ol, 1.7 equiv. of TFAA, 1.5 equiv. of DBU,0.1 equiv. of CuCl₂, CH₃CN, 0-25° C., 12 h., 75%) to provide thepropargyl ether S-6. S-6 is thermally cyclized (N,N-diethylaniline, 190°C., 0.5 h., 90%) to afford the intermediate benzopyran 60. 60 isreductively aminated (1.5 equiv. of 3-bromoaniline, THF, 70° C., 4 h.,90%, then 2.0 equiv. of NaCNBH₃, 10% MeOH, 70° C., 4 h., 83%) and theintermediate amine is acylated (1.3 equiv. of cyclopropanecarbonylchloride (C₃H₅COCl), 1.3 equiv. of Et₃N, 0.1 equiv. of 4-DMAP, CH₂Cl₂,25° C., 12 h., 85-95%) to provide the aryl bromide amide S-9. S-9 iscoupled to methyl acrylate by a palladium-mediated Heck reaction (4.0equiv. of methyl acrylate, 0.2 equiv. of Pd₂(dba)₃, 0.5 equiv. ofP(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 24 h., 80%) to afford compound 29.

Example 4 Preparation of Compounds 28, 29, 36, 42, 51-56, S-7 and S-8

The strategy employed for the preparation of Compounds 28, 29, 36, 42,51-56, S-7 and S-8 is shown below.

Thus, benzopyran aldehyde 60 is reductively aminated (1.5 equiv. ofmethyl 4-amino-benzoate, or ethyl 3-aminobenzoate, or methyl(4-aminomethyl)benzoate, THF, 70° C., 4 h., 70° C., then 2.0 equiv. ofNaCNBH₃, 10% MeOH, 70° C., 4 h., 77%-82%) and the intermediate amine isacylated (1.3 equiv. of cyclopropanecarbonyl chloride (C₃H₅COCl), 1.3equiv. of Et₃N, 0.1 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 12 h., 85-95%) toafford amides 51, 41 and 55, respectively. 51, 41 and 55 aresubsequently hydrolyzed (4.0 equiv. of LiOH, THF:H₂O (10:1), 25° C., 12h., 75%-98%) to provide the mono-acids 52, 36 and 56, respectively.

Similarly, the reductive amination product of benzopyran aldehyde 60, isacylated (1.3 equiv. of cyclopropanecarbonyl chloride (C₃H₅COCl), 1.3equiv. of Et₃N, 0.1 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 12 h., 85-95%) toprovide amides 53, 29 and S-7, respectively. 53, 29 and S7 arehydrolyzed (4.0 equiv. of LiOH, THF:H₂O (10:1), 25° C., 12 h., 75%-98%)to afford the mono-acids, 54, 28 and S-8, respectively.

Example 5 Preparation of Compounds 34, 45 and 47-49

The strategy employed for the preparation of Compounds 34, 45 and 47-49is shown below.

Thus, S-9 is coupled by a palladium-mediated Heck reaction (2.0 equiv.of acrylontrile or 2.0 equiv. of penta-2,4-dienoic acid methyl ester,0.2 equiv. of Pd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N,DMF, 90° C., 24 h., 55% and 70% and 85%) to afford compounds 34 and 45,respectively.

Similarly, S-9 is coupled by a palladium-mediated Heck reaction (2.0equiv. of 3-vinylbenzaldehyde, 0.2 equiv. of Pd₂(dba)₃, 0.6 equiv. ofP(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C. 24 h., 85%) to provide thecoupled benzaldehyde, which is oxidized (1.5 equiv. of NaClO₂, 4.0equiv. of NaH₂PO₄, 10 equiv. of 2-methyl-2-butene, THF:t-BuOH:H₂O(3:1:1), 25° C., 3 h., 98%) and the resulting acid is methylated (10.0equiv. of CH₂N₂, Et₂O, 0° C., 1 h., 100%) to provide the methyl ester48. S-9 also undergoes a palladium-mediated Suzuki reaction (5.0 equiv.of (3-methoxycarbonylphenyl)boronic acid or (4-methoxycarbonylphenyl)boronic acid, 0.2 equiv. of Pd(PPh₃)₄, toluene:MeOH:1M Na₂CO₃ (10:3:1),90° C., 24 h., 75% and 78%) to afford biphenyls 47 and 48, respectively.

Example 6 Preparation of Compounds 30-33, 35, 37-40, 42 and 43

The strategy for the preparation of Compounds 30-33, 35, 37-40, 42 and43 is shown below.

Thus, 29 is transesterified (0.5 equiv. of n-Bu₂Sn═O, EtOH, or i-PrOH,25° C., 48 h., 50% and 34%) to afford esters 30 and 31, respectively. 29is reduced (1.2 equiv. of diisobutylaluminum hydride (Dibal-H), toluene,−78° C., 0.5 h., 52%) to provide the allyl alcohol 32. 32 is O-allylated(2.0 equiv. of NaH, 3.0 equiv. of MeI, 0° C., 1 h., 95%), or is acylated(1.2 equiv. of MeOC(O)Cl, 2.0 equiv. of Et₃N, 0.1 equiv. of 4-DMAP,CH₂Cl₂, 25° C., 24 h., 90% or 1.2 equiv. of MeC(O)Cl, 2.0 equiv. ofEt₃N, 0.1 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 24 h., 90%) to affordcompounds 33, 42 and 43, respectively. 29 is hydrolyzed (4.0 equiv. ofLiOH, THF:H₂O (10:1), 25° C., 24 h. 88%) to the acid which is aminatedby mixed anhydride formation followed by exposure to an amine, (1.2equiv. of EtOC(O)Cl, 1.5 equiv. of Et₃N, 0.1 equiv. of 4-DMAP, CH₂Cl₂,25° C., 1 h., then 3.0 equiv. of NH₃, MeNH₂, PbNH₂ or ((CH₂)₅)N, CH₂Cl₂,25° C., 12 h., 85%-95%) to provide amides 37-40. 29 also undergoescyclopropanation (10.0 equiv. of CH₂N₂, 0.2 equiv. of Pd(OAc)₂, Et₂O,25° C., 12 h., 95%) to afford compound 35.

Representative procedures for the preparation of Region II modifiedcompounds are shown in Examples 7 and 8.

Example 7 Preparation of Compounds 61-77, 80-84, S-10 and S-11

The strategy employed for the preparation of 61-77, 80-84, S-10 and S-11is shown below.

Thus, benzopyran 60 is reductively aminated (2.0 equiv. of1-bromo-3-aminobenzene 130, THF, 70° C., 4 h., 70° C., then 2.0 equiv.of NaCNBH₃, 10% MeOH, 70° C., 4 h., 70%) and the intermediate aminecoupled to methyl acrylate via a palladium mediated Heck reaction (1.5equiv. of methyl acrylate, 0.2 equiv. of Pd₂(dba)₃, 0.5 equiv. ofP(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 24 h., 65%) to afford the amineS-10. S-10 is N-alkylated (5.0 equiv. of NaH, 5.0 equiv. of PhBr, PhI orMeBr, EtOH, 80° C., 70%-85%) to provide compounds 78 and 79,respectively. S-10 is also N-acylated (5.0 equiv. of an acid chloride(RCOCl), 5.0 equiv. of Et₃N, 0.2 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 24 h.55%-100%) to afford products 29, 61-77 and S-11. S-10 is furtherN-acylated (5.0 equiv. of an unsubstituted or substituted phenylisocyanate RNCO, 5.0 equiv. of Et₃N, CH₂Cl₂, 25° C., 24 h. 75%-85%) toprovide urea products 80 and 81, respectively. Finally, S-10 amine isN-acylated (5.0 equiv. of a substituted phenyl isothiocyanate RNCS, 5.0equiv. of Et₃N, CH₂Cl₂, 25° C., 24 h., 50%-70%) to afford the thioureaproducts 83 and 84.

Example 8 Preparation of Compounds 87, 94, 98-101, 103 and S-13

The strategy employed for the preparation of 87, 94, 98-101, 103 andS-13 is shown below.

Thus, amine S-12 is acylated (2.0 equiv. of benzoyl chloride, 2.0 equiv.of Et₃N, 0.2 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 24 h., 95%) to affordbenzopyran amide 103. 103 is oxidized (10 equiv. of DMDO, acetone, 0°C., 1 h., 100%) to provide epoxide S-13 (100%). S-13 undergoes ringopening (5.0 equiv. of PhSH, Amberlyst-15 catalyst, CH₂Cl₂, 25° C., 24h., 95%) to afford the alcohol-sulfide compound S-14. S-14 is acylated(2.0 equiv. of acetic anhydride, 2.0 equiv. of Et₃N, 0.2 equiv. of4-DMAP, CH₂Cl₂, 25° C., 24 h., 90%) to provide the acylated product,S-15. The acetate S-15 and the alcohol S-14 are coupled to methylacrylate via a Heck reaction (2.0 equiv. of methyl acrylate, 0.2 equiv.of Pd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C.,24 h., 70%-84%) to afford esters 98 and 99, respectively. Epoxide S-13undergoes ring opening (5.0 equiv. of piperidine, CH₂Cl₂, 25° C., 24 h.,90%) to afford the alcohol-amino compound S-16. S-16 is acylated (2.0equiv. of acetic anhydride, 2.0 equiv. of Et₃N, 0.2 equiv. of 4-DMAP,CH₂Cl₂, 25° C., 24 h., 90%) to provide the acylated product, S-17. Theacetate S-17 and the alcohol S-16 are coupled to methyl acrylate via aHeck reaction (2.0 equiv. of methyl acrylate, 0.2 equiv. of Pd₂(dba)₃,0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 24 h.,70%-84%) to afford esters 100 and 101, respectively. Similarly, epoxideS-13 undergoes ring opening (5.0 equiv. of H₂O, Amberlyst-15 catalyst,THF, 25° C., 48 h., 95%) to afford the diol S-18. S-18 is coupled tomethyl acrylate via a Heck reaction (2.0 equiv. of methyl acrylate, 0.2equiv. of Pd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF,90° C., 24 h., 70%-84%) to provide ester 94. Epoxide S-13 also undergoesring opening (2.0 equiv. of Et₂AlCN, CH₂Cl₂, 0° C., 1 h., 83%) andelimination (40% KOH:MeOH (1:2), 25° C., 24 h., 90%) to afford theconjugated cyano compound S-19. S-19 is coupled to methyl acrylate via aHeck reaction (2.0 equiv. of methyl acrylate, 0.2 equiv. of Pd₂(dba)₃,0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 24 h.,70%-84%) to provide ester 87.

Representative procedures for the preparation of Region III modifiedcompounds are shown in Examples 9 to 17.

Example 9 Preparation of Compounds 85, 93, 95, 102, S-20, S-21, S-22 andS-23

The strategy employed for the preparation of Compounds 85, 93, 95, 102,S-20, S-21, S-22 and S-23 is shown below.

Thus, benzopyran amide 103 is oxidized (0.02 equiv. of OsO₄, 2.0 equiv.of NMO, acetone, H₂O (10:1), 25° C., 24 h., 85%) to afford diol S-20.S-20 is diacylated (5.0 equiv. of acetic anhydride, 10.0 equiv. of Et₃N,0.2 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 24 h., 90%) to provide thediacetate S-21. The diol S-20 and the diacetate S-21 are coupled tomethyl acrylate via a Heck reaction (2.0 equiv. of methyl acrylate, 0.2equiv. of Pd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF,90° C., 24 h., 65%-80%) to afford esters 93 and 95, respectively.Intermediate benzopyran amide 103 is reduced (10% Pd/C, EtOAc, 25° C.,0.5 h., 100%) to afford amide S-22. S-22 is coupled to methyl acrylatevia a Heck reaction (2.0 equiv. of methyl acrylate, 0.2 equiv. ofPd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 24h., 65%-80%) to provide ester 85. Intermediate benzopyran amide 103 isalso cyclopropanated (CHCl3, 50% NaOH, (7:1), adogen 464 catalyst, 25°C., 6 h., 85%) to afford compound S-23. S-23 is coupled to methylacrylate via a Heck reaction (2.0 equiv. of methyl acrylate, 0.2 equiv.of Pd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C.,24 h., 65%-80%) to provide ester 102.

Example 10 Preparation of Compounds 110, 111, 114-118, 147 and 148

The strategy employed for the preparation of Compounds 110, 111,114-118, 147 and 148 is shown below.

Thus, 3-bromo-aniline 130 is acylated (1.1 equiv. of C₆H₁₁COCl, 1.3equiv. of Et₃N, 0.05 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 3 h., 95%) toafford amide 131. 131 is coupled to methyl acrylate via a Heck reaction(4.0 equiv. of methyl acrylate, 0.2 equiv. of Pd₂(dba)₃, 0.6 equiv. ofP(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 12 h., 80%) to provide ester132. 132 is N-alkylated (1.1 equiv. of NaH, THF, 0° C., 30 min., then1.3 equiv. of benzyl bromides, THF, 2 h., 60%-90% where R—X=methyliodide, benzyl bromide, 2-bromobenzyl bromide, 3-bromobenzyl bromide,4-bromobenzyl bromide, 4-tert-butyl benzyl bromide, 3-methoxy benzylbromide, 3,5-dimethoxy benzyl bromide, 3-(trifluoromethyl) benzylbromide, 2-naphthyl benzyl bromide) to afford compounds 105, 110-112,114-118 and 148.

Example 11 Preparation of Compounds 106-109

The strategy employed for the preparation of Compounds 106-109 is shownbelow.

Thus, aryl bromides 114 and 115 are coupled to tert-butyl acrylate via aHeck reaction (4.0 equiv. of tert-butyl acrylate, 0.2 equiv. ofPd₂(dba)₃, 0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 12h., 80%) to afford esters 109 and 110, respectively. 109 and 110 areacidified (20% TFA in CH₂Cl₂, 25° C., 1 h., 95%) to provide acids 108and 106, respectively.

Example 12 Preparation of Compounds 105 and 112

The strategy employed for the preparation of Compounds 105 and 112 isshown below.

Thus, 3-bromo-aniline 130 is N-acylated (1.1 equiv. of C₆H₁₁COCl, 1.3equiv. of Et₃N, 0.05 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 3 h., 95%) toafford amide 131. 131 is coupled to methyl acrylate via a Heck reaction(4.0 equiv. of methyl acrylate, 0.2 equiv. of Pd₂(dba)₃, 0.6 equiv. ofP(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 12 h., 80%) to provide ester132. 132 is N-acylated (1.1 equiv. of para-bromoC₆H₄COCl, 1.3 equiv. ofEt₃N, 0.05 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 3 h., 95%) to affordtertiary amide 112. 112 is coupled to tert-butyl acrylate via a Heckreaction (4.0 equiv. of tert-butyl acrylate, 0.2 equiv. of Pd₂(dba)₃,0.6 equiv. of P(o-tol)₃, 5.0 equiv. of Et₃N, DMF, 90° C., 12 h., 80%) toprovide diester 105.

Example 13 Preparation of Compounds 121-129

The strategy employed for the preparation of Compounds 121-129 is shownbelow.

Thus, aryl bromide 112 is coupled to para-substituted styrene via a Heckreaction (4.0 equiv. of styrene, or para-methoxy styrene, or paratert-butyl styrene, 0.05 equiv. of Pd₂(dba)₃, 0.15 equiv. of P(o-tol)₃,5.0 equiv. of Et₃N, DMF, 90° C., 12 h., 65%-80%) to afford esters 121,122 and 123, respectively. 112 is coupled to unsubstituted andsubstituted phenyl and thiophene via a Suzuki reaction (2.5 equiv. ofboronic acid, 0.2 equiv. of Pd(PPh₃)₄, toluene:MeOH:1M Na₂CO₃ (10:3:1),80° C., 12 h., 60%-80%) to provide compounds 124-129.

Example 14 Preparation of Compounds 105, 133, 134, 136-138, 159, 160 andS-24

The strategy employed for the preparation of Compounds 105, 133, 134,136-138, 159, 160 and S-24 is shown below.

Thus, para-bromobenzaldehyde is coupled to tert-butyl acrylate via aHeck reaction (4.0 equiv. of tert-butyl acrylate, 5.0 equiv. of Et₃N,0.05 equiv. of Pd₂(dba)₃, 0.15 equiv. of P(o-tol)₃, DMF, 90° C., 12 h.,85%) to afford aldehyde S-24. S-24 is reductively aminated (1.5 equiv.of 3-bromoaniline, 0.05 equiv. of AcOH, MeOH, 25° C., 30 min., then 1.7equiv. of NaCNBH₃, 1 h., 90%) to provide amine S-25, which is acylated(1.1 equiv. of C₆H₁₁COCl, 1.3 equiv. of Et₃N, 0.05 equiv. of 4-DMAP,CH₂Cl₂, 25° C., 3 h., 90%) to afford aryl bromide S-26. S-26 is coupledvia a Heck reaction (4.0 equiv. of acrylate or 4.0 equiv. of allylether, 5.0 equiv. of Et₃N, 0.05 equiv. of Pd₂(dba)₃, 0.15 equiv. ofP(o-tol)₃, DMF, 90° C., 12 h., 60%-85%) to provide compounds 105, 133,134 and 136-138.

Example 15 Preparation of Compounds 140-146 and S-28

The strategy employed for the preparation of Compounds 140-146 and S-28is shown below.

Thus, aldehyde S-24 is coupled to amine S-27 via a reductive amination(0.05 equiv. of AcOH, MeOH, 25° C., 30 min., then 1.2 equiv. of NaCNBH₃,25° C., 1 h., 85%) to afford amine S-28. S-28 is N-acylated (2.0 equiv.of acid chloride, 3.0 equiv. of Et₃N, 0.05 equiv. of 4-DMAP, CH₂Cl₂, 25°C., 1 h., 80%-95%) to provide compounds 105 and 140-144. S-28 is alsoacylated (2.0 equiv. of isocyanate, 3.0 equiv. of Et₃N, 0.05 equiv. of4-DMAP, CH₂Cl₂, 25° C., 1 h., 60%-80%) to afford urea compounds 145 and146.

Example 16 Preparation of Compounds 104, 105, 139 and 150-158

The strategy employed for the preparation of Compounds 104, 105, 139 and150-158 is shown below.

Thus, aryl bromide 112 is coupled to acrylates via a Heck reaction (4.0equiv. of acrylate, 5.0 equiv. of Et₃N, 0.05 equiv. of Pd₂(dba)₃, 0.15equiv. of P(o-tol)₃, DMF, 90° C., 12 h., 50%-80%) to afford compounds105 and 150-155. Ester 105 is hydrolyzed (20% TFA in CH₂Cl₂, 1 h., 25°C., 95%) to provide acid 104. Acid 104 is esterified (1.2 equiv. of DCC,10 equiv. of i-PrOH or BnOH, 0.2 equiv. of 4-DMAP, DMF, 25° C., 12 h.,60%) to afford compounds 152 and 153, respectively. Aryl bromide 112 iscoupled to alkenes via a Heck reaction (4.0 equiv. of methyl vinylether, ethyl vinyl ether and phenyl vinyl ether, 5.0 equiv. of Et₃N,0.05 equiv. of Pd₂(dba)₃, 0.15 equiv. of P(o-tol)₃, DMF, 90° C., 12 h.,50%-80%) to provide compounds 156 to 158, respectively. Further, arylbromide 112 is reduced (0.05 equiv. of 10% Pd/C, H₂ (1 atm.), EtOAc, 25°C., 30 min., 100%) to afford the saturated ester, which is coupled totert-butyl acrylate via a Heck reaction (4.0 equiv. of tert-butylacrylate, 5.0 equiv. of Et₃N, 0.05 equiv. of Pd₂(dba)₃, 0.15 equiv. ofP(o-tol)₃, DMF, 90° C., 12 h., 35%-75%) to provide compound 139.

Example 17 Preparation of Compounds 161-167 and S-29

The strategy employed for the preparation of Compounds 161-167 and S-29is shown below.

Thus, 2,4-dihydroxybenzaldehyde S-28 is selectively monoprotected (1.0equiv. of SEM-Cl, 1.2 equiv. of Et₃N, CH₂Cl₂, 25° C., 12 h., 75%) toafford the para hydroxyl compound S-29. S-29 is O-alkylated (1.05 equiv.of Tf₂O, 1.2 equiv. of Et₃N, CH₂Cl₂, 78° C., 1 h., 95%) and the triflateis coupled to tert-butyl acrylate via a Heck reaction (4.0 equiv. oftert-butyl acrylate, 5.0 equiv. of Et₃N, 0.05 equiv. of Pd₂(dba)₃, 0.15equiv. of P(o-tol)₃, DMF, 90° C., 12 h., 76%) to provide compound S-30.Aldehyde S-30 is coupled to amine S-27 via a reductive amination (1.2equiv. of S-27, 0.05 equiv. of AcOH, MeOH, 25° C., 1 h., then 1.5 equiv.of NaCNBH₃, 2 h., 80%) to afford amine S-31. S-31 is N-acylated (1.2equiv. of C₆H₁₁COCl, 1.5 equiv. of Et₃N, 0.05 equiv. of 4-DMAP, CH₂Cl₂,25° C., 4 h., 90%) to provide amide S-32. S-32 is deprotected (3.0equiv. of BnBr, 5.0 equiv. of K₂CO₃, DMF, 80° C., 12 h., 65%) to affordalcohol 161. 161 is alkylated with (3.0 equiv. of MeI, 5.0 equiv. ofK₂CO₃, DMF, 80° C., 12 h., 90%) to provide methyl ether 162; or with(3.0 equiv. of BnBr, 5.0 equiv. of K₂CO₃, DMF, 80° C., 12 h., 65%) toafford benzyl ether 163, or acetylated with (3.0 equiv. of BrCH₂COOEt,5.0 equiv. of K₂CO₃, DMF, 80° C., 12 h., 90%) to provide 167. Alcohol161 is O-alkylated (3.0 equiv. of AcCl, BzCl or MsCl, 5.0 equiv. ofEt₃N, CH₂Cl₂, 2 h., 70%-90%) to provide compounds 164, 165 and 166,respectively.

Example 18 Preparation of Compounds 121, 125, 126 and 174-264

The strategy employed for the preparation of Compounds 121, 125, 126 and174-264 is shown below.

Thus, Boc protected cinnamic acid 168 is immobilized on resin (1.0equiv. of Merrifield Resin, (0.91 mmol/mg), 2.0 equiv. of Cs₂CO₃, 0.5equiv. of TBAI, DMF, 55° C., 24 h.) to afford resin 169. 169 isdeprotected (20% TFA in CH₂Cl₂, 25° C., 1 h.) and the resultantresin-bound amine is reductively alkylated with 4-bromobenzaldehyde(10.0 equiv. of 4-aminobenzaldehyde, 0.05 equiv. of AcOH, THF:MeOH(2:1), 25° C., 1 h., then 8 equiv. of NaCNBH₃, THF:MeOH (2:1), 25° C., 2h.) to provide amino resin 170. 170 is acylated (for R¹COCl: 30 equiv.of R¹COCl, 40.0 equiv. of Et₃N, 1.0 equiv. of 4-DMAP, CH₂Cl₂, 25° C., 12h., for R¹NCO, 30.0 equiv. of R¹NCO, 40.0 equiv. of Et₃N, 1.0 equiv. of4-DMAP, DMF, 65° C., 60 h.) with one of three acyl groups to affordamide or urea resins 171. The acylated resins (171) were subjected toeither Heck coupling with thirteen substituted styrenes (as illustratedbelow; 8.0 equiv. of styrene, 10.0 equiv. of Et₃N, 0.5 equiv. ofPd₂(dba)₃, 1.5 equiv. of P(o-tol)₃, DMF, 90° C., 48 h.) or Suzukicoupling with eighteen boronic acids (as illustrated below; 5.0 equiv.of boronic acid, 3.0 equiv. of Cs₂CO₃, 0.5 equiv. of Pd(PPh₃)₄, DMF, 90°C., 24 h.) to provide stilbene resins 172 and biaryl resins 173,respectively.

Hydrolysis of these resins (172 and 173) with base (10.0 equiv. ofNaOMe, Et₂O:MeOH (10:1), 25° C., 20 min.) affords compounds 121, 125,126 and 174-264. Analysis of the library by LCMS after purificationshowed the average purity of these compounds to be >95%.

Example 19 Activation of FXR by Novel Compounds

To determine if the compounds identified as ligands could promote theassociation of FXR with co-activators in vitro, a fluorescence resonanceenergy transfer (FRET)-based coactivator binding assay was employed(see, for example, Makishima et al. (1999), supra, Urizar et al. (2002).A natural product that lowers cholesterol as an antagonist ligand forFXR. Science. 296(5573), 1703-6). This assay relies on anagonist-induced interaction between the nuclear receptor and itscoactivator bringing two fluorogenic partners together resulting in thenuclear receptor ligand-dependent FRET. Specific recruitment of apeptide containing the receptor binding domain of the steroid receptorco-activator SRC-1 (LXXLL) to the FXR ligand-binding domain was onlyobserved in the presence of the agonists fexaramine, fexarine, fexarene,SRI-1, SRI-2 and GW4064. GW4064 demonstrated the strongest recruitmentwith an EC₅₀ value of 100 nM followed by fexaramine (EC₅₀ 255 nM),fexarine (EC₅₀ 222 nM), and fexarene (EC₅₀≈255 nM). Weaker recruitmentis seen with compounds SRI-1 and SRI-2.

The ability of these compounds to activate the receptor in a number ofdifferent cell-based reporter gene assays was then determined. Therecently identified high affinity non-steroidal synthetic compoundGW4064 was used as a control in these experiments. CV-1 cells weretransiently transfected with an expression plasmid for mouse FXR andhuman RXR with a thymidine kinase (TK) minimal promoter reporter vectorcontaining either no copies or six copies of the ecdysone responseelement (ECRE), a well-characterized FXR response element (FXRE). Inaddition, two copies of the recently identified FXRE everted repeatseparated by 8 nucleotides (ER-8) was also studied (see, for example,Laffitte et al. (2000). Identification of the DNA binding specificityand potential target genes for the farnesoid X-activated receptor. JBiol Chem. 275(14), 10638-47; Kast et al. (2002). Regulation ofmultidrug resistance-associated protein 2 (ABCC2) by the nuclearreceptors pregnane X receptor, farnesoid X-activated receptor, andconstitutive androstane receptor. J Biol Chem. 277(4), 2908-15).

The cells were then treated with increasing concentrations offexaramine, fexarine, fexarene, SRI-1, SRI-2 or GW4064. Fexaramine,fexarine, fexarene and GW4064 showed robust activation of both of theFXREs (ECRE 100-fold; ER-8 4-fold) with a maximal activity achieved at 1μM (concentrations higher than 1 μM were tested but produced no moreactivity). The compounds SRI-1 and SRI-2, although structurally similarto fexaramine, showed little or no activity. Novel compounds idntifiedabove showed no activity on the minimal TK promoter. However, GW4064displayed a weak activity (less than 2 fold) on this promoter. Similarresults were found in a variety of different cell types including livercells (HEPG2) and kidney cells (HEK 293).

Having demonstrated that the newly identified compounds could robustlyactivate multiple copies of FXREs linked to a TK minimal promoter, theability of the compounds to activate natural promoters of known FXRtargets in a transient transfection cell-based assay was examined. Forthis study, the following gene promoters were used: intestinal bile acidbinding protein (IBABP; see, for example, Grober et al. (1999).Identification of a bile acid-responsive element in the human ileal bileacid-binding protein gene. Involvement of the farnesoid Xreceptor/9-cis-retinoic acid receptor heterodimer. J Biol Chem. 274(42),29749-54), phospholipid transfer protein (PLTP) (Urizar et al (2000).The farnesoid X-activated receptor mediates bile acid activation ofphospholipid transfer protein gene expression. J Biol Chem. 275(50),39313-7) and multidrug resistance related protein 2 (MRP-2) (Kast et al.(2002), supra), which are all well characterized targets of FXR. Thenatural promoters of both the IBABP and PLTP genes contain one copy ofan inverted repeat with a one base spacing (IR-1) while MRP-2 containsan ER-8 element. The results obtained were similar to experiments withmultiple FXRE copies with maximum efficacy of the fexaramine, fexarine,fexarene and GW4064 compounds observed at 1 μM, while SRI-1 and SRI-2showed little or no activity. The most robust activation (28-fold) wasseen on the IBABP promoter. Less robust (2-3 fold) but specificactivation was observed on the PLTP and MRP-2 promoters.

Example 20 Induction of FXR Target Genes by Novel Compounds

RNA Isolation and Northern Blot Hybridization

HepG2 or HT29-derived cell lines were typically cultured in mediumcontaining superstripped FBS for 24 hr before the addition of a ligandor DMSO (vehicle) for an additional 24-48 hr. Total RNA was isolatedusing TRIzol reagent and was resolved (10 μg/lane) on a 1% agarose, 2.2M formaldehyde gel, transferred to a nylon membrane (Hybond N⁺; AmershamBiosciences, Inc.), and cross-linked to the membrane with UV light.

cDNA probes were radiolabeled with [α-³²P]dCTP using the highprimelabeling kit (Amersham Biosciences, Inc.). Membranes were hybridizedusing the QuikHyb hybridization solution (Stratagene, La Jolla, Calif.)according to the manufacturer's protocol. Blots were normalized forvariations of RNA loading by hybridization to a control probe, either,18 S ribosomal cDNA, or the ribosomal protein 36B4. The RNA levels werequantitated using a PhosphorImager (ImageQuant software; MolecularDynamics, Inc., Sunnyvale, Calif.) in addition to being exposed to X-rayfilm.

RNA Analysis of FXR Target Genes

The liver and the intestinal system are the major areas where FXR playsa role in the induction of specific gene targets in response to bileacid (BA) concentrations. To establish that the identified compounds areeffective in studying the function of FXR in these systems, thecompounds were examined for their ability to induce characterized genetargets. In addition to the ability to induce characterized genetargets, invention compounds are also useful for identification of genetargets for FXR, i.e., genes which are modulated (i.e., induced orrepressed) by FXR.

Human colon cells HT29 (FXR null until differentiated) were infectedwith retroviral vectors that expressed either FXR constructs and thepuromycin-resistant gene or the puromycin-resistant gene alone.Puromycin resistant cells were isolated and pooled cell populations werepropagated that harbored either the vector alone (HT29-BABE),overexpressed FXR full length (HT29-FXRFL), a non-functional FXRtruncated at the AF2 region (HT29-FXR-AF2), or a constitutively activeFXR that has the VP16 activation domain fused N-terminal of the protein(HT29-VP16-FXR). Confirmation of the successful establishment of thedifferent stable cell lines was established via northern blot analysisof FXR message levels in the cells.

HT29-BABE lines do not express FXR while the stable cell lines expressedthe exogenous FXR message. To test the ability of these cell lines toinduce FXR target genes total RNA was isolated from cells treatedovernight with increasing amounts of CDCA or GW4064. Northern blotanalysis of the HT29-FXRFL cell line showed robust concentrationdependent induction of IBABP mRNA by both CDCA and GW4064. Maximalactivation of the IBABP gene by CDCA was observed at 100 μM while only 1μM of GW4064 was needed to achieve the same level of induction. Noinduction of IBABP mRNA levels was observed in the HT29-BABE orHT29-FXR-AF2 cell lines. Constitutive expression was seen in theHT29-VP16-FXR and was super-induced by addition of CDCA and GW4064.These observations verify the usefulness of this colon cell model systemfor studying the induction of FXR target genes.

The ability of the novel compounds identified herein to induce IBABPgene expression in this cell system was also examined. Total RNA fromHT29 stable cells treated overnight with fexaramine, fexarine andfexarene was probed for IBABP gene expression. Fexaramine, fexarine andfexarene all induced expression of the IBABP mRNA in the HT29-FXRFL withsimilar profiles to that seen for GW4064 (maximal activity at 1 μMconcentration). No induction was seen in the HT29-BABE or HT29-FXR-AF2cell lines, proving the specificity of the compounds. These resultsdemonstrate that the novel compounds of the present invention areeffective in studying FXR target genes in an intestinal model cellsystem.

To demonstrate the usefulness of these compounds in studying FXRfunction in the liver, a model hepatocyte cell system that expresses theFXR gene was employed (Kast et al. (2002), supra). Confluent HEPG2-FXRcells were treated overnight with increasing concentrations offexaramine, fexarine, fexarene SRI-1, SRI-2 and the control ligandsGW4064 and CDCA. Total RNA was isolated and the expression of the FXRtarget genes SHP, MRP-2, BSEP and PLTP was measured by Northern blotanalysis.

The control ligands CDCA and GW4064 showed similar induction of thetarget genes to what has been previously reported. Of the novelcompounds identified herein, fexaramine was the most effective inducerof target genes, although strong induction was also observed withfexarine and fexarene. In this hepatocyte cell system, maximalactivation of FXR target genes by these compounds was achieved at 10 μM,which is similar to the control ligand GW4064. Interestingly, althoughGW4064 showed slightly better induction of the FXR target genes PLTP andSHP, fexaramine matched GW4064 induced activation of the BSEP and MRP-2genes. These results demonstrate that these novel compounds can be usedto identify and characterize new FXR target genes in the liver and theintestinal cell systems. Differences in efficacy of target geneinduction between the liver and the intestinal cell systems may reflectthe ability of the liver hepatocytes to mount a xenobotic response orcell specific permeability to the identified compounds. Modification ofthe ligands to overcome these effects may be made in order to increasethe efficacy of these drugs in liver cell systems.

Further evidence that invention compounds can be used to identify andcharacterize additional FXR gene targets is provided by the large scalescreening summarized in Appendix 1 (for genes upregulated by inventioncompounds) and Appendix 2 (for genes downregulated by inventioncompounds).

It will be apparent to those skilled in the art that various changes maybe made in the invention without departing from the spirit and scopethereof, and therefore, the invention encompasses embodiments inaddition to those specifically disclosed in the specification, but onlyas indicated in the appended claims.

APPENDIX 1

Up Regulated Genes with Treatment Fex: Accession Fold Change Number(Fex/DMSO) Gene Description NM_004617 11.90 “HOMO SAPIENS TRANSMEMBRANE4 SUPERFAMILY MEMBER 4 (TM4SF4), MRNA.” NM_003195 10.29 “HOMO SAPIENSTRANSCRIPTION ELONGATION FACTOR A (SII), 2 (TCEA2), MRNA.” NM_0008939.17 “HOMO SAPIENS KININOGEN (KNG), MRNA.” NM_138961 6.12 “HOMO SAPIENSSIMILAR TO ENDOTHELIAL CELL-SELECTIVE ADHESION MOLECULE (ESAM), MRNA”NM_139284 4.53 “HOMO SAPIENS LEUCINE-RICH REPEAT LGI FAMILY, MEMBER 4(LGI4), MRNA” AP000501 4.12 “HOMO SAPIENS GENOMIC DNA, CHROMOSOME8P11.2, CLONE: 91H23 TO 9-41” NM_000394 3.96 “HOMO SAPIENS CRYSTALLIN,ALPHA A (CRYAA), MRNA.” BM701748 3.78 UI-E-CQ1-AEW-L-18-0-UI.R1 HOMOSAPIENS CDNA 5′ END NM_006209 3.64 “HOMO SAPIENS ECTONUCLEOTIDEPYROPHOSPHATASE/PHOSPHODIESTERASE 2 (AUTOTAXIN) (ENPP2), MRNA.”NM_018602 3.39 “HOMO SAPIENS DNAJ (HSP40) HOMOLOG, SUBFAMILY A, MEMBER 4(DNAJA4), MRNA” AA442232 3.32 “ZV60H08.R1 SOARES_TESTIS_NHT HOMO SAPIENSCDNA CLONE IMAGE: 758079 5′, MRNA SEQUENCE” NM_031916 3.28 “HOMO SAPIENSAKAP-ASSOCIATED SPERM PROTEIN (ASP), MRNA.” NM_022148 3.15 “HOMO SAPIENSCYTOKINE RECEPTOR-LIKE FACTOR 2 (CRLF2), MRNA” NM_024935 3.14 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ13687 (FLJ13687), MRNA” NM_032866 3.11“HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ14957 (FLJ14957), MRNA.” NM_0324713.02 “HOMO SAPIENS PROTEIN KINASE (CAMP-DEPENDENT, CATALYTIC) INHIBITORBETA (PKIB), MRNA.” NM_013370 3.00 “HOMO SAPIENS PREGNANCY-INDUCEDGROWTH INHIBITOR (OKL38), MRNA.” AL163259 2.99 NULL NM_000151 2.83 “HOMOSAPIENS GLUCOSE-6-PHOSPHATASE, CATALYTIC (GLYCOGEN STORAGE DISEASE TYPEI, VON GIERKE DISEASE) (G6PC), MRNA.” NM_020689 2.78 “HOMO SAPIENSSODIUM CALCIUM EXCHANGER (NCKX3), MRNA.” NM_021098 2.71 “HOMO SAPIENSCALCIUM CHANNEL, VOLTAGE-DEPENDENT, ALPHA 1H SUBUNIT (CACNA1H), MRNA”NM_024984 2.67 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ12193 (FLJ12193),MRNA” NM_021778 2.65 “HOMO SAPIENS A DISINTEGRIN AND METALLOPROTEINASEDOMAIN 28 (ADAM28), TRANSCRIPT VARIANT 2, MRNA.” AF123462 2.59 “HOMOSAPIENS BAC526N18 NEUREXIN III GENE, PARTIAL CDS” 129456.1 2.59 NULLAB020858 2.56 “HOMO SAPIENS GENOMIC DNA OF 8P21.3-P22 ANTI-ONCOGENE OFHEPATOCELLULAR COLORECTAL AND NON-SMALL CELL LUNG CANCER, SEGMENT 1/11”NM_016445 2.56 “HOMO SAPIENS PLECKSTRIN 2 (MOUSE) HOMOLOG (PLEK2),MRNA.” NM_003614 2.53 “HOMO SAPIENS GALANIN RECEPTOR 3 (GALR3), MRNA.”NM_145047 2.49 “HOMO SAPIENS OXIDORED-NITRO DOMAIN-CONTAINING PROTEIN(NOR1), MRNA” NM_001552 2.45 “HOMO SAPIENS INSULIN-LIKE GROWTH FACTORBINDING PROTEIN 4 (IGFBP4), MRNA” AB002366 2.42 “HUMAN MRNA FOR KIAA0368GENE, PARTIAL CDS” NM_031957 2.41 “HOMO SAPIENS KERATIN ASSOCIATEDPROTEIN 1.5 (KRTAP1.5), MRNA” NM_020659 2.38 “HOMO SAPIENS TWEETYHOMOLOG 1 (DROSOPHILA) (TTYH1), MRNA.” AB028998 2.37 “HOMO SAPIENS MRNAFOR KIAA1075 PROTEIN, PARTIAL CDS” NM_001678 2.36 “HOMO SAPIENS ATPASE,NA+/K+ TRANSPORTING, BETA 2 POLYPEPTIDE (ATP1B2), MRNA.” NM_014375 2.35“HOMO SAPIENS FETUIN B (FETUB), MRNA.” NM_000361 2.33 “HOMO SAPIENSTHROMBOMODULIN (THBD), MRNA.” NM_004259 2.33 “HOMO SAPIENS RECQPROTEIN-LIKE 5 (RECQL5), MRNA.” NM_000106 2.33 “HOMO SAPIENS CYTOCHROMEP450, SUBFAMILY IID (DEBRISOQUINE, SPARTEINE, ETC., -METABOLIZING),POLYPEPTIDE 6 (CYP2D6), MRNA.” NM_003742 2.31 “HOMO SAPIENS ATP-BINDINGCASSETTE, SUB-FAMILY B (MDR/TAP), MEMBER 11 (ABCB11), MRNA.” NM_0030442.28 “HOMO SAPIENS SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTERTRANSPORTER, BETAINE/GABA), MEMBER 12 (SLC6A12), MRNA.” NM_001546 2.27“HOMO SAPIENS INHIBITOR OF DNA BINDING 4, DOMINANT NEGATIVEHELIX-LOOP-HELIX PROTEIN (ID4), MRNA” AF069061 2.25 “HOMO SAPIENSGLCNAC-1-P TRANSFERASE GENE, EXONS 1 THROUGH 4” NM_012444 2.25 “HOMOSAPIENS SPO11 MEIOTIC PROTEIN COVALENTLY BOUND TO DSB-LIKE (S.CEREVISIAE) (SPO11), MRNA” NM_000901 2.24 “HOMO SAPIENS NUCLEAR RECEPTORSUBFAMILY 3, GROUP C, MEMBER 2 (NR3C2), MRNA.” AK027705 2.22 “HOMOSAPIENS CDNA FLJ14799 FIS, CLONE NT2RP4001351, WEAKLY SIMILAR TO HUMANOVARIAN CANCER DOWNREGULATED MYOSIN HEAVY CHAIN HOMOLOG (DOC1) MRNA”NM_052890 2.20 “HOMO SAPIENS PEPTIDOGLYCAN RECOGNITION PROTEIN LPRECURSOR (PGLYRP), MRNA” NM_018379 2.19 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ11280 (FLJ11280), MRNA” NM_005434 2.19 “HOMO SAPIENS BENEPROTEIN (BENE), MRNA” NM_004183 2.18 “HOMO SAPIENS VITELLIFORM MACULARDYSTROPHY (BEST DISEASE, BESTROPHIN) (VMD2), MRNA” NM_005141 2.18 “HOMOSAPIENS FIBRINOGEN, B BETA POLYPEPTIDE (FGB), MRNA.” NM_001496 2.16“HOMO SAPIENS GDNF FAMILY RECEPTOR ALPHA 3 (GFRA3), MRNA.” NM_0032402.15 “HOMO SAPIENS ENDOMETRIAL BLEEDING ASSOCIATED FACTOR (LEFT- RIGHTDETERMINATION, FACTOR A; TRANSFORMING GROWTH FACTOR BETA SUPERFAMILY)(EBAF), MRNA.” NM_032413 2.14 “HOMO SAPIENS NORMAL MUCOSA OF ESOPHAGUSSPECIFIC 1 (NMES1), MRNA” BC035779 2.14 “HOMO SAPIENS, SIMILAR TO SOLUTECARRIER FAMILY 9 (SODIUM/HYDROGEN EXCHANGER), ISOFORM 7, CLONE MGC:46316 IMAGE: 5590356, MRNA, COMPLETE CDS” NM_021949 2.13 “HOMO SAPIENSATPASE, CA++ TRANSPORTING, PLASMA MEMBRANE 3 (ATP2B3), MRNA.” BE3484042.12 “HW17D06.X1 HOMO SAPIENS CDNA, 3′ END” NM_021233 2.12 “HOMO SAPIENSDNASE II-LIKE ACID DNASE (DLAD), TRANSCRIPT VARIANT 1, MRNA” NM_0046692.12 “HOMO SAPIENS CHLORIDE INTRACELLULAR CHANNEL 3 (CLIC3), MRNA.”NM_015685 2.12 “HOMO SAPIENS SYNDECAN BINDING PROTEIN (SYNTENIN) 2(SDCBP2), MRNA.” NM_014945 2.11 “HOMO SAPIENS KIAA0843 PROTEIN(KIAA0843), MRNA.” X98507 2.11 H. SAPIENS MRNA FOR MYOSIN-I BETAAK056268 2.11 “HOMO SAPIENS CDNA FLJ31706 FIS, CLONE NT2RI2006210,MODERATELY SIMILAR TO MUS MUSCULUS SHD MRNA” AL137400 2.10 HOMO SAPIENSMRNA; CDNA DKFZP434L162 (FROM CLONE DKFZP434L162) NM_000808 2.09 “HOMOSAPIENS GAMMA-AMINOBUTYRIC ACID (GABA) A RECEPTOR, ALPHA 3 (GABRA3),MRNA.” 1387891.1 2.09 NULL AF260225 2.08 “HOMO SAPIENS TESTIN 2 ANDTESTIN 3 GENES, COMPLETE CDS, ALTERNATIVELY SPLICED” NM_007163 2.08“HOMO SAPIENS SOLUTE CARRIER FAMILY 14 (UREA TRANSPORTER), MEMBER 2(SLC14A2), MRNA.” AB046859 2.08 “HOMO SAPIENS MRNA FOR KIAA1639 PROTEIN,PARTIAL CDS” NM_002022 2.07 “HOMO SAPIENS FLAVIN CONTAININGMONOOXYGENASE 4 (FMO4), MRNA.” NM_000366 2.06 “HOMO SAPIENS TROPOMYOSIN1 (ALPHA) (TPM1), MRNA” NM_021146 2.06 “HOMO SAPIENS ANGIOPOIETIN-LIKEFACTOR (CTD6), MRNA.” NM_031961 2.06 “HOMO SAPIENS KERATIN ASSOCIATEDPROTEIN 9.2 (KRTAP9.2), MRNA” NM_005971 2.06 “HOMO SAPIENS FXYDDOMAIN-CONTAINING ION TRANSPORT REGULATOR 3 (FXYD3), TRANSCRIPT VARIANT1, MRNA” AK026600 2.05 “HOMO SAPIENS CDNA: FLJ22947 FIS, CLONE KAT09234”NM_012277 2.05 “HOMO SAPIENS PANCREATIC BETA CELL GROWTH FACTOR (INGAP),MRNA.” S71547 2.04 “{ECCDNA 24, EXTRACHROMOSOMAL CIRCULAR DNA} [HUMAN,HELA S3 CELLS, GENOMIC, 806 NT]” NM_002625 2.04 “HOMO SAPIENS6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6- BIPHOSPHATASE 1 (PFKFB1), MRNA.”U71218 2.04 “HUMAN CLONE C74F4, 24KB PROXIMAL CMT1A-REP SEQUENCE”AA427982 2.03 “HUMAN KRUPPEL RELATED ZINC FINGER PROTEIN (HTF10) MRNA,COMPLETE CDS.” NM_014242 2.02 “HOMO SAPIENS ZINC FINGER PROTEIN 237(ZNF237), MRNA.” AF070586 2.02 HOMO SAPIENS CLONE 24528 MRNA SEQUENCENM_000482 2.01 “HOMO SAPIENS APOLIPOPROTEIN A-IV (APOA4), MRNA” M308942.00 “GNL|UG|HS#S3370 HUMAN T-CELL RECEPTOR TI REARRANGED GAMMA CHAINMRNA V-J-C REGION, COMPLETE CDS/CDS = (140, 1156)/ GB = M30894/GI =339406/UG = HS.112259/LEN = 1586” BC016979 2.00 “HOMO SAPIENS, CLONEMGC: 21802 IMAGE: 4181575, MRNA, COMPLETE CDS” NM_002666 1.99 “HOMOSAPIENS PERILIPIN (PLIN), MRNA.” NM_144659 1.98 “HOMO SAPIENS T-COMPLEX10A-2 (LOC140290), MRNA” NM_006160 1.97 “HOMO SAPIENS NEUROGENICDIFFERENTIATION 2 (NEUROD2), MRNA.” AL137581 1.97 HOMO SAPIENS MRNA;CDNA DKFZP434B0610 (FROM CLONE DKFZP434B0610); PARTIAL CDS BC024316 1.97“HOMO SAPIENS, CLONE IMAGE: 3912859, MRNA” AL049328 1.97 HOMO SAPIENSMRNA; CDNA DKFZP564E026 (FROM CLONE DKFZP564E026) NM_017734 1.96 “HOMOSAPIENS PALMDELPHIN (PALMD), MRNA.” AK022620 1.96 “HOMO SAPIENS CDNAFLJ12558 FIS, CLONE NT2RM4000787” NM_000873 1.95 “HOMO SAPIENSINTERCELLULAR ADHESION MOLECULE 2 (ICAM2), MRNA” U84003 1.95 “HOMOSAPIENS BRIDGING INTEGRATOR PROTEIN-1 (BIN1) GENE, EXONS 7-12” NM_0529621.95 “HOMO SAPIENS CLASS II CYTOKINE RECEPTOR (IL22RA2), MRNA” NM_0155771.95 “HOMO SAPIENS RETINOIC ACID INDUCED 14 (RAI14), MRNA.” NM_1446261.93 “HOMO SAPIENS HYPOTHETICAL PROTEIN MGC17299 (MGC17299), MRNA”AF217965 1.93 HOMO SAPIENS CLONE PP102 UNKNOWN MRNA NM_002701 1.93 “HOMOSAPIENS POU DOMAIN, CLASS 5, TRANSCRIPTION FACTOR 1 (POU5F1), MRNA.”NM_031418 1.93 “HOMO SAPIENS CHROMOSOME 11 OPEN READING FRAME 25(C11ORF25), MRNA.” NM_013391 1.93 “HOMO SAPIENS DIMETHYLGLYCINEDEHYDROGENASE PRECURSOR (DMGDH), MRNA.” U82670 1.93 “HOMO SAPIENS XQ28OF HIGH-MOBILITY GROUP PROTEIN 17 RETROPSEUDOGENE (PSHMG17), COMPLETESEQUENCE; AND MELANOMA ANTIGEN FAMILY A1 (MAGEA1) AND ZINC FINGERPROTEIN 275 (ZNF275) GENES, COMPLETE CDS” NM_000964 1.93 “HOMO SAPIENSRETINOIC ACID RECEPTOR, ALPHA (RARA), MRNA” S70612 1.92 “GLYCINETRANSPORTER TYPE 1C {ALTERNATIVELY SPLICED} [HUMAN, SUBSTANTIA NIGRA,MRNA, 2202 NT]” AK021786 1.92 “HOMO SAPIENS CDNA FLJ11724 FIS, CLONEHEMBA1005331” Y15067 1.91 HOMO SAPIENS MRNA FOR ZN-FINGER PROTEIN ZNF232AL110262 1.91 HOMO SAPIENS MRNA; CDNA DKFZP586F0221 (FROM CLONEDKFZP586F0221) Z64378 1.91 “H. SAPIENS CPG ISLAND DNA GENOMIC MSE1FRAGMENT, CLONE 114F7, REVERSE READ CPG114F7.RT1A” AW963947 1.91EST376020 HOMO SAPIENS CDNA NM_001767 1.91 “HOMO SAPIENS CD2 ANTIGEN(P50), SHEEP RED BLOOD CELL RECEPTOR (CD2), MRNA” U41384 1.91 “HUMANSMALL NUCLEAR RIBONUCLEAR PROTEIN ASSOCIATED POLYPEPTIDE N (SNRPN) GENEAND PRADER-WILLI SYNDROME GENE, COMPLETE SEQUENCE.” NM_012320 1.90 “HOMOSAPIENS LYSOPHOSPHOLIPASE 3 (LYSOSOMAL PHOSPHOLIPASE A2) (LYPLA3), MRNA”AB011116 1.90 “HOMO SAPIENS MRNA FOR KIAA0544 PROTEIN, PARTIAL CDS”NM_018915 1.89 “HOMO SAPIENS PROTOCADHERIN GAMMA SUBFAMILY A, 2(PCDHGA2), TRANSCRIPT VARIANT 1, MRNA” NM_003157 1.89 “HOMO SAPIENSSERINE/THREONINE KINASE 2 (STK2), MRNA.” NM_004072 1.89 “HOMO SAPIENSCHEMOKINE-LIKE RECEPTOR 1 (CMKLR1), MRNA.” AK001546 1.89 “HOMO SAPIENSCDNA FLJ10684 FIS, CLONE NT2RP3000220” NM_014151 1.88 “HOMO SAPIENSHSPC053 PROTEIN (HSPC053), MRNA” 449023.1 1.88 NULL NM_032259 1.88 “HOMOSAPIENS HYPOTHETICAL PROTEIN DKFZP434F054 (DKFZP434F054), MRNA”NM_001169 1.88 “HOMO SAPIENS AQUAPORIN 8 (AQP8), MRNA.” X79535 1.88“HUMAN MRNA FOR BETA TUBULIN, CLONE NUK_278.” U10689 1.87 “HUMAN MAGE-5AANTIGEN (MAGE5A) GENE, COMPLETE CDS” AF324499 1.87 “HOMO SAPIENSOLFACTORY-LIKE RECEPTOR MRNA, COMPLETE CDS” AL133659 1.87 HOMO SAPIENSMRNA; CDNA DKFZP434K0227 (FROM CLONE DKFZP434K0227); PARTIAL CDSNM_032962 1.86 “HOMO SAPIENS SMALL INDUCIBLE CYTOKINE SUBFAMILY A(CYS-CYS), MEMBER 14 (SCYA14), TRANSCRIPT VARIANT 2, MRNA.” BC0131811.86 “HOMO SAPIENS, CLONE MGC: 21682 IMAGE: 4385873, MRNA, COMPLETE CDS”NM_019038 1.86 “HOMO SAPIENS HYPOTHETICAL PROTEIN (FLJ11045), MRNA.”W89128 1.86 “ZH69C04.S1 HOMO SAPIENS CDNA, 3′ END” 1327919.2 1.85 NULLNM_005165 1.85 “HOMO SAPIENS ALDOLASE C, FRUCTOSE-BISPHOSPHATE (ALDOC),MRNA.” NM_014037 1.85 “HOMO SAPIENS NTT5 PROTEIN (NTT5), MRNA.” H105291.85 “YM04A08.R1 HOMO SAPIENS CDNA, 5′ END” NM_032687 1.85 PROTEIN OFUNKNOWN FUNCTION AJ292466 1.84 “HOMO SAPIENS MRNA FOR WDR9 PROTEIN (WDR9GENE), FORM B” NM_002190 1.84 “HOMO SAPIENS INTERLEUKIN 17 (CYTOTOXICT-LYMPHOCYTE- ASSOCIATED SERINE ESTERASE 8) (IL17), MRNA.” AF191622 1.84“HOMO SAPIENS FILAMIN (FLNB) GENE, EXON 35” NM_052863 1.84 “HOMO SAPIENSSECRETOGLOBIN, FAMILY 3A, MEMBER 1 (SCGB3A1), MRNA” 201531.1 1.84 NULLNM_001727 1.83 “HOMO SAPIENS BOMBESIN-LIKE RECEPTOR 3 (BRS3), MRNA”X63578 1.83 H. SAPIENS GENE FOR PARVALBUMIN NM_014897 1.83 “HOMO SAPIENSKIAA0924 PROTEIN (KIAA0924), MRNA.” NM_031200 1.83 “HOMO SAPIENSCHEMOKINE (C-C MOTIF) RECEPTOR 9 (CCR9), TRANSCRIPT VARIANT A, MRNA.”AL157504 1.83 HOMO SAPIENS MRNA; CDNA DKFZP586O0724 (FROM CLONEDKFZP586O0724) BC031087 1.83 “HOMO SAPIENS, SIMILAR TOGAMMA-AMINOBUTYRIC-ACID RECEPTOR GAMMA-1 SUBUNIT PRECURSOR (GABA(A)RECEPTOR), CLONE MGC: 33838 IMAGE: 5289008, MRNA, COMPLETE CDS”NM_014461 1.81 “HOMO SAPIENS CONTACTIN 6 (CNTN6), MRNA.” AB047819 1.81“HOMO SAPIENS GCMA/GCM1 GENE FOR CHORION-SPECIFIC TRANSCRIPTION FACTORGCMA, COMPLETE CDS” NM_003264 1.81 “HOMO SAPIENS TOLL-LIKE RECEPTOR 2(TLR2), MRNA.” NM_000508 1.81 “HOMO SAPIENS FIBRINOGEN, A ALPHAPOLYPEPTIDE (FGA), TRANSCRIPT VARIANT ALPHA-E, MRNA.” AK021635 1.81“HOMO SAPIENS CDNA FLJ11573 FIS, CLONE HEMBA1003376” NM_032211 1.80“HOMO SAPIENS LYSYL OXIDASE-LIKE 4 (LOXL4), MRNA” NM_033014 1.80 “HOMOSAPIENS OSTEOGLYCIN (OSTEOINDUCTIVE FACTOR, MIMECAN) (OGN), TRANSCRIPTVARIANT 1, MRNA.” AB020636 1.80 “HOMO SAPIENS MRNA FOR KIAA0829 PROTEIN,PARTIAL CDS” AJ242910 1.80 HOMO SAPIENS MRNA FOR N-ACETYLGLUCOSAMINEKINASE X52852 1.80 HUMAN CYCLOPHILIN-RELATED PROCESSED PSEUDOGENENM_014069 1.80 “HOMO SAPIENS SPR1 PROTEIN (SPR1), MRNA.” NM_032607 1.80“HOMO SAPIENS CREB/ATF FAMILY TRANSCRIPTION FACTOR (CREB-H), MRNA”1462881.1 1.79 “MEMBER OF THE RHODOPSIN FAMILY OF G PROTEIN-COUPLEDRECEPTORS (GPCR), HAS MODERATE SIMILARITY TO OLFACTORY RECEPTOR 41(MOUSE OLFR41), WHICH MAY HAVE A ROLE IN OLFACTORY RESPONSE ANDINTERACTS PREFERENTIALLY WITH HEPTANAL” AF300796 1.79 “HOMO SAPIENSSIALIC ACID-SPECIFIC 9-O-ACETYLESTERASE I MRNA, COMPLETE CDS” NM_0062041.79 “HOMO SAPIENS PHOSPHODIESTERASE 6C, CGMP-SPECIFIC, CONE, ALPHAPRIME (PDE6C), MRNA.” NM_033066 1.79 “HOMO SAPIENS MEMBRANE PROTEIN,PALMITOYLATED 4 (MAGUK P55 SUBFAMILY MEMBER 4) (MPP4), MRNA” NM_0003411.79 “HOMO SAPIENS SOLUTE CARRIER FAMILY 3 (CYSTINE, DIBASIC AND NEUTRALAMINO ACID TRANSPORTERS, ACTIVATOR OF CYSTINE, DIBASIC AND NEUTRAL AMINOACID TRANSPORT), MEMBER 1 (SLC3A1), MRNA.” 1452359.3 1.78 NULL AL0801031.78 HOMO SAPIENS MRNA; CDNA DKFZP564N2216 (FROM CLONE DKFZP564N2216)D86992 1.78 “HOMO SAPIENS IMMUNOGLOBULIN LAMBDA GENE LOCUS DNA, CLONE:123E1 UPSTREAM CONTIG” NM_021038 1.78 “HOMO SAPIENS MUSCLEBLIND-LIKE(DROSOPHILA) (MBNL), MRNA.” 958731.1 1.78 “MEMBER OF THE SHORT-CHAINDEHYDROGENASE-REDUCTASE FAMILY, HAS A REGION OF LOW SIMILARITY TO 11BETA- HYDROXYSTEROID DEHYDROGENASE (MOUSE HSD11B1), WHICH IS AMICROSOMAL CARBONYL REDUCTASE THAT HAS 11 BETA- DEHYDROGENASE AND 11-OXOREDUCTASE ACTIVITY” NM_021135 1.77 “HOMO SAPIENS RIBOSOMAL PROTEIN S6KINASE, 90 KD, POLYPEPTIDE 2 (RPS6KA2), MRNA” NM_000773 1.77 “HOMOSAPIENS CYTOCHROME P450, SUBFAMILY IIE (ETHANOL- INDUCIBLE) (CYP2E),MRNA.” NM_000487 1.77 “HOMO SAPIENS ARYLSULFATASE A (ARSA), MRNA.”AL049431 1.77 HOMO SAPIENS MRNA; CDNA DKFZP586J211 (FROM CLONEDKFZP586J211) AW406117 1.76 “HUMAN LAMBDA CLONE 247 FRA3B REGION DNA,CYCLOPHILIN PSEUDOGENE, PARTIAL SEQUENCE, AND HPV16 VIRAL INTEGRATIONSITE.” NM_002934 1.76 “HOMO SAPIENS RIBONUCLEASE, RNASE A FAMILY, 2(LIVER, EOSINOPHIL-DERIVED NEUROTOXIN) (RNASE2), MRNA” NM_001347 1.76“HOMO SAPIENS DIACYLGLYCEROL KINASE, THETA (110 KD) (DGKQ), MRNA”AB023173 1.76 “HOMO SAPIENS MRNA FOR KIAA0956 PROTEIN, PARTIAL CDS”BC025726 1.76 “HOMO SAPIENS, POTASSIUM CHANNEL, SUBFAMILY K, MEMBER 17(TASK-4), CLONE MGC: 34117 IMAGE: 5201326, MRNA, COMPLETE CDS” AB0015171.76 “HOMO SAPIENS DNA FOR TMEM1 PROTEIN, PWP2 PROTEIN, KNP-I ALPHAPROTEIN AND KNP-I BETA PROTEIN, PARTIAL AND COMPLETE CDS” U28480 1.76“HUMAN UNCOUPLING PROTEIN (UCP) MRNA, COMPLETE CDS” NM_002881 1.75 “HOMOSAPIENS V-RAL SIMIAN LEUKEMIA VIRAL ONCOGENE HOMOLOG B (RAS RELATED; GTPBINDING PROTEIN) (RALB), MRNA.” NM_021871 1.75 “HOMO SAPIENS FIBRINOGEN,A ALPHA POLYPEPTIDE (FGA), TRANSCRIPT VARIANT ALPHA, MRNA” NM_0329891.75 “HOMO SAPIENS BCL2-ANTAGONIST OF CELL DEATH (BAD), TRANSCRIPTVARIANT 2, MRNA.” NM_003960 1.75 “HOMO SAPIENS KIDNEY-AND LIVER-SPECIFICGENE (CML1), MRNA.” NM_014693 1.75 “HOMO SAPIENS ENDOTHELIN CONVERTINGENZYME 2 (ECE2), MRNA.” NM_001323 1.74 “HOMO SAPIENS CYSTATIN E/M(CST6), MRNA.” AL832363 1.74 HOMO SAPIENS MRNA; CDNA DKFZP451N156 (FROMCLONE DKFZP451N156) NM_003272 1.74 “HOMO SAPIENS TRANSMEMBRANE 7SUPERFAMILY MEMBER 1 (UPREGULATED IN KIDNEY) (TM7SF1), MRNA.” NM_0050181.74 “HOMO SAPIENS PROGRAMMED CELL DEATH 1 (PDCD1), MRNA.” AK057674 1.74“HOMO SAPIENS CDNA FLJ33112 FIS, CLONE TRACH2001109” AI797481 1.74WE88E01.X1 HOMO SAPIENS CDNA 3′ END NM_014965 1.74 “HOMO SAPIENSKIAA1042 PROTEIN (KIAA1042), MRNA.” NM_004570 1.73 “HOMO SAPIENSPHOSPHOINOSITIDE-3-KINASE, CLASS 2, GAMMA POLYPEPTIDE (PIK3C2G), MRNA.”AK025583 1.73 “HOMO SAPIENS CDNA: FLJ21930 FIS, CLONE HEP04301, HIGHLYSIMILAR TO HSU90916 HUMAN CLONE 23815 MRNA SEQUENCE” 1397221.43 1.73NULL AF345906 1.73 “HOMO SAPIENS LIM MINERALIZATION PROTEIN 3 MRNA,COMPLETE CDS” NM_032642 1.73 “HOMO SAPIENS WINGLESS-TYPE MMTVINTEGRATION SITE FAMILY, MEMBER 5B (WNT5B), TRANSCRIPT VARIANT 1, MRNA.”1329470.331 1.73 NULL M61170 1.73 “HUMAN POLYMORPHIC EPITHELIAL MUCIN(PEM) GENE, COMPLETE CDS” NM_000627 1.73 “HOMO SAPIENS LATENTTRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN 1 (LTBP1), MRNA.”NM_145276 1.72 “HOMO SAPIENS SIMILAR TO KRUPPEL-TYPE ZINC FINGER (C2H2)(LOC147837), MRNA” 1353408.4 1.72 NULL AF052160 1.72 HOMO SAPIENS CLONE24629 MRNA SEQUENCE NM_002600 1.72 “HOMO SAPIENS PHOSPHODIESTERASE 4B,CAMP-SPECIFIC (PHOSPHODIESTERASE E4 DUNCE HOMOLOG, DROSOPHILA) (PDE4B),MRNA.” D28877 1.72 “HOMO SAPIENS HNRPA2B1 GENE FOR HNRNP PROTEIN A2 ANDB1, COMPLETE CDS” AK022354 1.71 “HOMO SAPIENS CDNA FLJ12292 FIS, CLONEMAMMA1001812” NM_003734 1.71 “HOMO SAPIENS AMINE OXIDASE, COPPERCONTAINING 3 (VASCULAR ADHESION PROTEIN 1) (AOC3), MRNA.” NM_004921 1.71“HOMO SAPIENS CHLORIDE CHANNEL, CALCIUM ACTIVATED, FAMILY MEMBER 3(CLCA3), MRNA” BC034709 1.71 “HOMO SAPIENS, SIMILAR TO GAP JUNCTIONBETA-4 PROTEIN (CONNEXIN 30.3) (CX30.3), CLONE MGC: 21116 IMAGE:4755173, MRNA, COMPLETE CDS” NM_014912 1.71 “HOMO SAPIENS KIAA0940PROTEIN (KIAA0940), MRNA.” NM_018639 1.70 “HOMO SAPIENS CSBOX-CONTAINING WD PROTEIN (LOC55884), MRNA.” 979318.3 1.70 “PROTEINCONTAINING 11 LEUCINE RICH REPEATS, WHICH MEDIATE PROTEIN-PROTEININTERACTIONS, HAS A REGION OF LOW SIMILARITY TO HUMAN IGFALS, WHICH ISACID-LABILE SUBUNIT OF THE INSULIN- LIKE GROWTH FACTOR (IGF) BINDINGPROTEIN THAT MAY MODULATE IGF ACTIVITY” AK024603 1.70 “HOMO SAPIENSCDNA: FLJ20950 FIS, CLONE ADSE01927” NM_022370 1.70 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ21044 SIMILAR TO RBIG1 (FLJ21044), MRNA”NM_014954 1.70 “HOMO SAPIENS KIAA0985 PROTEIN (KIAA0985), MRNA.” M644971.70 “HUMAN APOLIPOPROTEIN AI REGULATORY PROTEIN (ARP-1) MRNA, COMPLETECDS” AB032986 1.70 “HOMO SAPIENS MRNA FOR KIAA1160 PROTEIN, PARTIAL CDS”AK094585 1.70 “HOMO SAPIENS CDNA FLJ37266 FIS, CLONE BRAMY2011280”NM_018592 1.69 “HOMO SAPIENS HYPOTHETICAL PROTEIN PRO0800 (PRO0800),MRNA” AF222345 1.69 “HOMO SAPIENS SUPPRESSOR OF FUSED VARIANT 3 MRNA,ALTERNATIVELY SPLICED, COMPLETE CDS” AJ420504 1.69 HOMO SAPIENS MRNAFULL LENGTH INSERT CDNA CLONE EUROIMAGE 2069692 NM_001656 1.69 “HOMOSAPIENS ADP-RIBOSYLATION FACTOR DOMAIN PROTEIN 1, 64 KD (ARFD1),TRANSCRIPT VARIANT ALPHA, MRNA.” AA868513 1.69 “AK43C02.S1 HOMO SAPIENSCDNA, 3′ END” NM_012400 1.69 “HOMO SAPIENS PHOSPHOLIPASE A2, GROUP IID(PLA2G2D), MRNA.” NM_003662 1.69 “HOMO SAPIENS PIRIN (PIR), MRNA.”U41302 1.69 “HUMAN CHROMOSOME 16 CREATINE TRANSPORTER (SLC6A8) AND (CDM)PARALOGOUS GENES, COMPLETE CDS” AU133056 1.69 “AU133056 HOMO SAPIENSCDNA, 5′ END” AB040903 1.69 “HOMO SAPIENS MRNA FOR KIAA1470 PROTEIN,PARTIAL CDS” U17081 1.69 “HUMAN FATTY ACID BINDING PROTEIN (FABP3) GENE,COMPLETE CDS.” AB029001 1.68 “HOMO SAPIENS MRNA FOR KIAA1078 PROTEIN,PARTIAL CDS” J03040 1.68 “HUMAN SPARC/OSTEONECTIN MRNA, COMPLETE CDS”AK024251 1.68 “HOMO SAPIENS CDNA FLJ14189 FIS, CLONE NT2RP2006184,HIGHLY SIMILAR TO HOMO SAPIENS MRNA FOR KIAA0918 PROTEIN” NM_004286 1.68“HOMO SAPIENS GTP BINDING PROTEIN 1 (GTPBP1), MRNA” NM_005980 1.68 “HOMOSAPIENS S100 CALCIUM BINDING PROTEIN P (S100P), MRNA.” NM_005953 1.68“METALLOTHIONEIN 2A, FUNCTIONS IN METAL HOMEOSTASIS AND PROTECTS AGAINSTHEAVY-METAL TOXICITY, MAY HAVE ROLES IN THE REGULATION OF CELLULARPROLIFERATION, APOPTOSIS, AND MALIGNANT PROGRESSION” AF195513 1.68 “HOMOSAPIENS PUR-GAMMA A-FORM (PURG) MRNA, COMPLETE CDS” NM_003546 1.68 “HOMOSAPIENS H4 HISTONE FAMILY, MEMBER K (H4FK), MRNA” NM_000869 1.67 “HOMOSAPIENS 5-HYDROXYTRYPTAMINE (SEROTONIN) RECEPTOR 3A (HTR3A), MRNA.”218630.6 1.67 PROTEIN OF UNKNOWN FUNCTION NM_000217 1.67 “HOMO SAPIENSPOTASSIUM VOLTAGE-GATED CHANNEL, SHAKER- RELATED SUBFAMILY, MEMBER 1(EPISODIC ATAXIA WITH MYOKYMIA) (KCNA1), MRNA.” AB033030 1.67 “HOMOSAPIENS MRNA FOR KIAA1204 PROTEIN, PARTIAL CDS” BC012362 1.67 “HOMOSAPIENS, CLONE MGC: 20484 IMAGE: 4650072, MRNA, COMPLETE CDS” AA0013341.67 “ZH83C02.R1 HOMO SAPIENS CDNA, 5′ END” NM_001114 1.67 “HOMO SAPIENSADENYLATE CYCLASE 7 (ADCY7), MRNA.” NM_006759 1.67 “HOMO SAPIENSUDP-GLUCOSE PYROPHOSPHORYLASE 2 (UGP2), MRNA.” NM_152270 1.67 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ34922 (FLJ34922), MRNA” NM_025206 1.67“HOMO SAPIENS FER-1-LIKE 4 (C. ELEGANS) (FER1L4), MRNA” NM_031305 1.66“HOMO SAPIENS HYPOTHETICAL PROTEIN DKFZP564B1162 (DKFZP564B1162), MRNA”H09245 1.66 “YL98A12.S1 HOMO SAPIENS CDNA, 3′ END” 1042260.1 1.66 NULLNM_004950 1.66 “HOMO SAPIENS DERMATAN SULFATE PROTEOGLYCAN 3 (DSPG3),MRNA.” AB007969 1.66 “HOMO SAPIENS MRNA, CHROMOSOME 1 SPECIFICTRANSCRIPT KIAA0500” NM_000705 1.66 “HOMO SAPIENS ATPASE, H+/K+EXCHANGING, BETA POLYPEPTIDE (ATP4B), MRNA.” NM_002965 1.66 “HOMOSAPIENS S100 CALCIUM BINDING PROTEIN A9 (CALGRANULIN B) (S100A9), MRNA”NM_006149 1.66 “HOMO SAPIENS LECTIN, GALACTOSIDE-BINDING, SOLUBLE, 4(GALECTIN 4) (LGALS4), MRNA” AL163248 1.66 HOMO SAPIENS CHROMOSOME 21SEGMENT HS21C048 AF009640 1.66 “HOMO SAPIENS CLONE 33IMMUNOGLOBULIN-LIKE TRANSCRIPT 5 PROTEIN MRNA, COMPLETE CDS” NM_0177861.66 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ20366 (FLJ20366), MRNA.”AF217796 1.66 “HOMO SAPIENS SCG10 LIKE-PROTEIN, HELICASE-LIKE PROTEINNHL, M68, AND ADP-RIBOSYLATION FACTOR RELATED PROTEIN 1 (ARFRP1) GENES,COMPLETE CDS” NM_015230 1.66 “HOMO SAPIENS CENTAURIN, DELTA 1 (CENTD1),MRNA.” NM_000802 1.66 “HOMO SAPIENS FOLATE RECEPTOR 1 (ADULT) (FOLR1),TRANSCRIPT VARIANT 1, MRNA” BC014851 1.66 “HOMO SAPIENS, SIMILAR TOLUNATIC FRINGE GENE HOMOLOG (DROSOPHILA), CLONE MGC: 22145 IMAGE:4453156, MRNA, COMPLETE CDS” AK000789 1.66 “HOMO SAPIENS CDNA FLJ20782FIS, CLONE COL03841” NM_006810 1.66 “HOMO SAPIENS FOR PROTEIN DISULFIDEISOMERASE-RELATED (PDIR), MRNA.” NM_030984 1.65 “HOMO SAPIENSTHROMBOXANE A SYNTHASE 1 (PLATELET, CYTOCHROME P450, SUBFAMILY V)(TBXAS1), TRANSCRIPT VARIANT TXS-II, MRNA.” NM_145016 1.65 “HOMO SAPIENSHYPOTHETICAL PROTEIN MGC24009 (MGC24009), MRNA” AK002122 1.65 “HOMOSAPIENS CDNA FLJ11260 FIS, CLONE PLACE1009060, WEAKLY SIMILAR TO BRO1PROTEIN” AB006627 1.65 “HOMO SAPIENS MRNA FOR KIAA0289 GENE, PARTIALCDS” AK022892 1.65 “HOMO SAPIENS CDNA FLJ12830 FIS, CLONE NT2RP2003073”AF088219 1.65 “HUMAN CC CHEMOKINE GENE CLUSTER, COMPLETE SEQUENCE.”BC035035 1.65 “HOMO SAPIENS, SIMILAR TO ECTONUCLEOTIDEPYROPHOSPHATASE/PHOSPHODIESTERASE 5, CLONE MGC: 33971 IMAGE: 5259487,MRNA, COMPLETE CDS” AF147791 1.65 “HOMO SAPIENS MUCIN 11 (MUC11) MRNA,PARTIAL CDS” AU127911 1.65 AU127911 HOMO SAPIENS CDNA 5′ END L13738 1.65“HOMO SAPIENS ACTIVATED P21CDC42HS KINASE (ACK1) MRNA, COMPLETE CDS”U78027 1.65 “HOMO SAPIENS BRUTON'S TYROSINE KINASE (BTK), ALPHA-D-GALACTOSIDASE A (GLA), L44-LIKE RIBOSOMAL PROTEIN (L44L) AND FTP3 (FTP3)GENES, COMPLETE CDS” AB037770 1.65 “HOMO SAPIENS MRNA FOR KIAA1349PROTEIN, PARTIAL CDS” AK025586 1.65 “HOMO SAPIENS CDNA: FLJ21933 FIS,CLONE HEP04337” NM_138569 1.65 “HOMO SAPIENS HYPOTHETICAL PROTEINMGC18257 (MGC18257), MRNA” AB011542 1.65 “HOMO SAPIENS MRNA FOR MEGF9,PARTIAL CDS” NM_015644 1.64 “HOMO SAPIENS DKFZP434B103 PROTEIN(DKFZP434B103), MRNA.” NM_012472 1.64 “HOMO SAPIENS TESTIS SPECIFICLEUCINE RICH REPEAT PROTEIN (TSLRP), MRNA.” NM_031371 1.64 “HOMO SAPIENSRBP1-LIKE PROTEIN (BCAA), TRANSCRIPT VARIANT 2, MRNA.” AI766221 1.64“WH68B09.X1 HOMO SAPIENS CDNA, 3′ END” NM_003878 1.64 “HOMO SAPIENSGAMMA-GLUTAMYL HYDROLASE (CONJUGASE, FOLYLPOLYGAMMAGLUTAMYL HYDROLASE)(GGH), MRNA.” NM_000761 1.64 “HOMO SAPIENS CYTOCHROME P450, SUBFAMILY I(AROMATIC COMPOUND-INDUCIBLE), POLYPEPTIDE 2 (CYP1A2), MRNA.” AL1375951.64 HOMO SAPIENS MRNA; CDNA DKFZP434P0810 (FROM CLONE DKFZP434P0810)AL543586 1.64 AL543586 HOMO SAPIENS CDNA AW276618 1.64 “XR17C08.X1 HOMOSAPIENS CDNA, 3′ END” AK023156 1.64 “HOMO SAPIENS CDNA FLJ13094 FIS,CLONE NT2RP3002163” NM_022768 1.64 “HOMO SAPIENS RNA BINDING MOTIFPROTEIN 15 (RBM15), MRNA” NM_007150 1.64 “HOMO SAPIENS ZINC FINGERPROTEIN 185 (LIM DOMAIN) (ZNF185), MRNA.” AK024371 1.64 “HOMO SAPIENSCDNA FLJ14309 FIS, CLONE PLACE3000221” AP003115 1.63 “HOMO SAPIENSGENOMIC DNA, CHROMOSOME 8Q23, CLONE: KB1000E4” 1401244.3 1.63 NULLNM_000033 1.63 “HOMO SAPIENS ATP-BINDING CASSETTE, SUB-FAMILY D (ALD),MEMBER 1 (ABCD1), MRNA.” NM_005542 1.63 “HOMO SAPIENS INSULIN INDUCEDGENE 1 (INSIG1), MRNA.” NM_004374 1.63 “HOMO SAPIENS CYTOCHROME COXIDASE SUBUNIT VIC (COX6C), NUCLEAR GENE ENCODING MITOCHONDRIALPROTEIN, MRNA” NM_017878 1.63 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ20556 (FLJ20556), MRNA.” NM_006214 1.63 “HOMO SAPIENS PHYTANOYL-COAHYDROXYLASE (REFSUM DISEASE) (PHYH), MRNA.” NM_006918 1.63 “HOMO SAPIENSSTEROL-C5-DESATURASE (ERG3 DELTA-5- DESATURASE HOMOLOG, FUNGAL)-LIKE(SC5DL), MRNA” NM_014629 1.63 “HOMO SAPIENS RHO GUANINE NUCLEOTIDEEXCHANGE FACTOR (GEF) 10 (ARHGEF10), MRNA.” U63721 1.63 “HUMAN ELASTIN(ELN) GENE, PARTIAL CDS, AND LIM-KINASE (LIMK1) GENE, COMPLETE CDS.”AU129688 1.63 AU129688 HOMO SAPIENS CDNA 5′ END AL122040 1.63 HOMOSAPIENS MRNA; CDNA DKFZP434G1972 (FROM CLONE DKFZP434G1972) AL1632631.63 NULL NM_014029 1.63 “HOMO SAPIENS HSPC022 PROTEIN (HSPC022), MRNA”NM_003554 1.62 “HOMO SAPIENS OLFACTORY RECEPTOR, FAMILY 1, SUBFAMILY E,MEMBER 2 (OR1E2), MRNA” NM_015074 1.62 “HOMO SAPIENS KINESIN FAMILYMEMBER 1B (KIF1B), MRNA.” BC002575 1.62 “HOMO SAPIENS, CLONE IMAGE:3161568, MRNA, PARTIAL CDS” NM_014131 1.62 “HOMO SAPIENS PRO0514 PROTEIN(PRO0514), MRNA” AL163277 1.62 NULL 1455058.1 1.62 NULL NM_022792 1.62“HOMO SAPIENS MATRIX METALLOPROTEINASE 19 (MMP19), TRANSCRIPT VARIANTRASI-9, MRNA.” NM_020344 1.62 “HOMO SAPIENS SOLUTE CARRIER FAMILY 24(SODIUM/POTASSIUM/CALCIUM EXCHANGER), MEMBER 2 (SLC24A2), MRNA”NM_003980 1.62 “HOMO SAPIENS MICROTUBULE-ASSOCIATED PROTEIN 7 (MAP7),MRNA.” S57283 1.62 “HOMO SAPIENS ENDOTHELIN ET-B RECEPTOR MRNA, COMPLETECDS” NM_006564 1.62 “HOMO SAPIENS G PROTEIN-COUPLED RECEPTOR (TYMSTR),MRNA.” BC011693 1.62 “HOMO SAPIENS, CLONE IMAGE: 3140802, MRNA” AF1176151.62 “HOMO SAPIENS HEME-BINDING PROTEIN (HBP) MRNA, COMPLETE CDS”NM_002196 1.62 “HOMO SAPIENS INSULINOMA-ASSOCIATED 1 (INSM1), MRNA.”1044035.1 1.61 NULL NM_000438 1.61 “HOMO SAPIENS PAIRED BOX GENE 3(WAARDENBURG SYNDROME 1) (PAX3), TRANSCRIPT VARIANT PAX3A, MRNA”NM_002405 1.61 “HOMO SAPIENS MANIC FRINGE HOMOLOG (DROSOPHILA) (MFNG),MRNA.” NM_006113 1.61 “HOMO SAPIENS VAV 3 ONCOGENE (VAV3), MRNA.”AL080148 1.61 HOMO SAPIENS MRNA; CDNA DKFZP434B204 (FROM CLONEDKFZP434B204); PARTIAL CDS AK056569 1.61 “HOMO SAPIENS CDNA FLJ32007FIS, CLONE NT2RP7009481, WEAKLY SIMILAR TO DROSOPHILA MELANOGASTERDISPATCHED MRNA” NM_018104 1.61 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ10474 (FLJ10474), MRNA.” NM_012339 1.61 “HOMO SAPIENS TRANSMEMBRANE 4SUPERFAMILY MEMBER (TETRASPAN NET-7) (NET-7), MRNA.” NM_001684 1.61“HOMO SAPIENS ATPASE, CA++ TRANSPORTING, PLASMA MEMBRANE 4 (ATP2B4),MRNA” NM_016098 1.61 “HOMO SAPIENS HSPC040 PROTEIN (LOC51660), MRNA.”NM_002997 1.61 “HOMO SAPIENS SYNDECAN 1 (SDC1), MRNA.” AF098485 1.61“HOMO SAPIENS NAPSIN 2 PRECURSOR, MRNA, PARTIAL SEQUENCE” NM_006672 1.61“HOMO SAPIENS SOLUTE CARRIER FAMILY 22 (ORGANIC ANION TRANSPORTER),MEMBER 7 (SLC22A7), MRNA.” BG476978 1.61 “HUMAN GENE FOR RYUDOCAN COREPROTEIN, EXON1-5, COMPLETE CDS.” AL133568 1.61 HOMO SAPIENS MRNA; CDNADKFZP434N197 (FROM CLONE DKFZP434N197) NM_005588 1.60 “HOMO SAPIENSMEPRIN A, ALPHA (PABA PEPTIDE HYDROLASE) (MEP1A), MRNA.” NM_003943 1.60“HOMO SAPIENS GENETHONIN 1 (GENX-3414), MRNA.” AC006017 1.60 “HUMANALR-LIKE PROTEIN MRNA, COMPLETE CDS.” AL080186 1.60 HOMO SAPIENS MRNA;CDNA DKFZP564B0769 (FROM CLONE DKFZP564B0769); PARTIAL CDS BC003417 1.60“HOMO SAPIENS, NADH DEHYDROGENASE (UBIQUINONE) 1 ALPHA SUBCOMPLEX, 10(42 KD), CLONE MGC: 5103 IMAGE: 3451514, MRNA, COMPLETE CDS” NM_0066011.60 “HOMO SAPIENS UNACTIVE PROGESTERONE RECEPTOR, 23 KD (P23), MRNA”AF218941 1.60 “HOMO SAPIENS CLONE W39395 FORMIN 2-LIKE PROTEIN MRNA,PARTIAL CDS” AA702323 1.60 “ZI83E03.S1 HOMO SAPIENS CDNA, 3′ END”NM_001082 1.60 “HOMO SAPIENS CYTOCHROME P450, SUBFAMILY IVF, POLYPEPTIDE2 (CYP4F2), MRNA” NM_017726 1.60 “HOMO SAPIENS PROTEIN PHOSPHATASE 1,REGULATORY (INHIBITOR) SUBUNIT 14D (PPP1R14D), MRNA” AA263106 1.60“HUMAN NUCLEIC ACID BINDING PROTEIN GENE, COMPLETE CDS.” NM_003038 1.59“HOMO SAPIENS SOLUTE CARRIER FAMILY 1 (GLUTAMATE/NEUTRAL AMINO ACIDTRANSPORTER), MEMBER 4 (SLC1A4), MRNA.” NM_030788 1.59 “HOMO SAPIENSDC-SPECIFIC TRANSMEMBRANE PROTEIN (LOC81501), MRNA” AP000506 1.59 “HOMOSAPIENS GENOMIC DNA, CHROMOSOME 6P21.3, HLA CLASS I REGION, SECTION5/20” NM_025012 1.59 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ13769(FLJ13769), MRNA” NM_000659 1.59 “HOMO SAPIENS AUTOIMMUNE REGULATOR(AUTOMIMMUNE POLYENDOCRINOPATHY CANDIDIASIS ECTODERMAL DYSTROPHY)(AIRE), TRANSCRIPT VARIANT 3, MRNA.” NM_004046 1.59 “HOMO SAPIENS ATPSYNTHASE, H+ TRANSPORTING, MITOCHONDRIAL F1 COMPLEX, ALPHA SUBUNIT,ISOFORM 1, CARDIAC MUSCLE (ATP5A1), MRNA” NM_021905 1.59 “HOMO SAPIENSGAMMA-AMINOBUTYRIC ACID (GABA) B RECEPTOR, 1 (GABBR1), TRANSCRIPTVARIANT 4, MRNA.” NM_000054 1.59 “HOMO SAPIENS ARGININE VASOPRESSINRECEPTOR 2 (NEPHROGENIC DIABETES INSIPIDUS) (AVPR2), MRNA.” NM_0209971.59 “HOMO SAPIENS LEFT-RIGHT DETERMINATION, FACTOR B (LEFTB), MRNA”NM_005044 1.59 “HOMO SAPIENS PROTEIN KINASE, X-LINKED (PRKX), MRNA.”AI807896 1.59 “HUMAN MYOSIN-IXB MRNA, COMPLETE CDS.” NM_001897 1.59“HOMO SAPIENS CHONDROITIN SULFATE PROTEOGLYCAN 4 (MELANOMA-ASSOCIATED)(CSPG4), MRNA.” NM_013937 1.59 “HOMO SAPIENS OLFACTORY RECEPTOR, FAMILY11, SUBFAMILY A, MEMBER 1 (OR11A1), MRNA.” NM_003830 1.59 “HOMO SAPIENSSIALIC ACID BINDING IG-LIKE LECTIN 5 (SIGLEC5), MRNA.” NM_006274 1.59“HOMO SAPIENS SMALL INDUCIBLE CYTOKINE SUBFAMILY A (CYS-CYS), MEMBER 19(SCYA19), MRNA.” AL049365 1.59 HOMO SAPIENS MRNA; CDNA DKFZP586A0618(FROM CLONE DKFZP586A0618) NM_002980 1.59 “HOMO SAPIENS SECRETINRECEPTOR (SCTR), MRNA.” Y11710 1.59 “H. SAPIENS MRNA FOR EXTRACELLULARMATRIX PROTEIN COLLAGEN TYPE XIV, C-TERMINUS” AB040928 1.59 “HOMOSAPIENS MRNA FOR KIAA1495 PROTEIN, PARTIAL CDS” BC022416 1.59 “HOMOSAPIENS, CLONE IMAGE: 4243767, MRNA” NM_001103 1.58 “HOMO SAPIENSACTININ, ALPHA 2 (ACTN2), MRNA.” S79669 1.58 “STEROIDOGENIC ACUTEREGULATOY PROTEIN [HUMAN, FOLLICLE CELLS, MRNA, 1641 NT]” 1001739.3 1.58NULL Z62748 1.58 “H. SAPIENS CPG ISLAND DNA GENOMIC MSE1 FRAGMENT, CLONE72E12, REVERSE READ CPG72E12.RT1A” NM_001313 1.58 “HOMO SAPIENSCOLLAPSIN RESPONSE MEDIATOR PROTEIN 1 (CRMP1), MRNA.” NM_000428 1.58“HOMO SAPIENS LATENT TRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN 2(LTBP2), MRNA.” NM_020653 1.58 “HOMO SAPIENS ZINC FINGER PROTEIN 287(ZNF287), MRNA” NM_024301 1.58 “HOMO SAPIENS FUKUTIN-RELATED PROTEIN(FKRP), MRNA” AK023517 1.58 “HOMO SAPIENS CDNA FLJ13455 FIS, CLONEPLACE1003256” NM_006188 1.58 “HOMO SAPIENS ONCOMODULIN (OCM), MRNA”BC011682 1.58 “HOMO SAPIENS, SIMILAR TO CATHEPSIN F, CLONE MGC: 19716IMAGE: 3535532, MRNA, COMPLETE CDS” AB017915 1.58 “HOMO SAPIENS MRNA FORCHONDROITIN 6-SULFOTRANSFERASE, COMPLETE CDS” NM_002461 1.58 “HOMOSAPIENS MEVALONATE (DIPHOSPHO) DECARBOXYLASE (MVD), MRNA.” 1503660.51.58 NULL BC023566 1.57 “HOMO SAPIENS, SIMILAR TO HYPOTHETICAL PROTEINFLJ31614, CLONE MGC: 20726 IMAGE: 4138119, MRNA, COMPLETE CDS” NM_0166151.57 “HOMO SAPIENS SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTERTRANSPORTER, GABA), MEMBER 13 (SLC6A13), MRNA.” NM_006540 1.57 “HOMOSAPIENS NUCLEAR RECEPTOR COACTIVATOR 2 (NCOA2), MRNA.” U45432 1.57“HUMAN ETV6 GENE, PROMOTER REGION AND PARTIAL CDS” NM_014056 1.57 “HOMOSAPIENS DKFZP564K247 PROTEIN (DKFZP564K247), MRNA.” NM_014191 1.57 “HOMOSAPIENS SODIUM CHANNEL, VOLTAGE GATED, TYPE VIII, ALPHA POLYPEPTIDE(SCN8A), MRNA” 240937.12 1.57 “PROTEIN OF UNKNOWN FUNCTION, HAS HIGHSIMILARITY TO UNCHARACTERIZED MOUSE 4931408A02RIK” X07855 1.57 “HUMANGENE FOR ALPHA-SUBUNIT OF GI2 EXON 9, A GTP-BINDING SIGNAL TRANSDUCTIONPROTEIN” NM_001748 1.57 “HOMO SAPIENS CALPAIN 2, (M/II) LARGE SUBUNIT(CAPN2), MRNA.” NM_024492 1.57 “HOMO SAPIENS APOLIPOPROTEIN (A) RELATEDGENE C (APOARGC), TRANSCRIPT VARIANT 1, MRNA” AB023185 1.57 “HOMOSAPIENS MRNA FOR KIAA0968 PROTEIN, PARTIAL CDS” NM_007036 1.57 “HOMOSAPIENS ENDOTHELIAL CELL-SPECIFIC MOLECULE 1 (ESM1), MRNA.” D11086 1.57HUMAN MRNA FOR INTERLEUKIN 2 RECEPTOR GAMMA CHAIN AB014581 1.57 “HOMOSAPIENS MRNA FOR KIAA0681 PROTEIN, PARTIAL CDS” NM_001994 1.57 “HOMOSAPIENS COAGULATION FACTOR XIII, B POLYPEPTIDE (F13B), MRNA” NM_0181621.57 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ10633 (FLJ10633), MRNA.”BC000429 1.57 “HOMO SAPIENS, CHROMOSOME 14 OPEN READING FRAME 2, CLONEMGC: 8356 IMAGE: 2819801, MRNA, COMPLETE CDS” AF060568 1.57 “HUMANPROMYELOCYTIC LEUKEMIA ZINC FINGER PROTEIN (PLZF) GENE, COMPLETE CDS.”NM_020980 1.57 “HOMO SAPIENS AQUAPORIN 9 (AQP9), MRNA.” S72487 1.56“ORF1 5′ TO PD-ECGF/TP...ORF2 5′ TO PD-ECGF/TP [HUMAN, EPIDERMOIDCARCINOMA CELL LINE A431, MRNA, 3 GENES, 1718 NT]” NM_006934 1.56 “HOMOSAPIENS SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GLYCINE),MEMBER 9 (SLC6A9), MRNA.” NM_006006 1.56 “HOMO SAPIENS ZINC FINGERPROTEIN 145 (KRUPPEL-LIKE, EXPRESSED IN PROMYELOCYTIC LEUKEMIA)(ZNF145), MRNA.” NM_002652 1.56 “HOMO SAPIENS PROLACTIN-INDUCED PROTEIN(PIP), MRNA.” NM_000707 1.56 “HOMO SAPIENS ARGININE VASOPRESSIN RECEPTOR1B (AVPR1B), MRNA” NM_000908 1.56 “HOMO SAPIENS NATRIURETIC PEPTIDERECEPTOR C/GUANYLATE CYCLASE C (ATRIONATRIURETIC PEPTIDE RECEPTOR C)(NPR3), MRNA.” AB033096 1.56 “HOMO SAPIENS MRNA FOR KIAA1270 PROTEIN,PARTIAL CDS” AL137558 1.56 HOMO SAPIENS MRNA; CDNA DKFZP434L1020 (FROMCLONE DKFZP434L1020) BI759599 1.56 “603047034F1 HOMO SAPIENS CDNA, 5′END” AK023849 1.56 “HOMO SAPIENS CDNA FLJ13787 FIS, CLONE PLACE4000670”1116941.1 1.56 NULL NM_019003 1.56 “HOMO SAPIENS SPINDLIN-LIKE(LOC54466), MRNA” NM_031488 1.56 “HOMO SAPIENS HYPOTHETICAL PROTEINDKFZP761I141 (DKFZP761I141), MRNA” AB032947 1.56 “HOMO SAPIENS MRNA FORKIAA1121 PROTEIN, PARTIAL CDS” AF057177 1.56 HOMO SAPIENS T-CELLRECEPTOR GAMMA VI GENE REGION NM_007072 1.56 “HOMO SAPIENS HERV-HLTR-ASSOCIATING 2 (HHLA2), MRNA” NM_001145 1.56 “HOMO SAPIENSANGIOGENIN, RIBONUCLEASE, RNASE A FAMILY, 5 (ANG), MRNA.” AF287967 1.55“HOMO SAPIENS HOMEOBOX B7 (HOXB7) GENE, PARTIAL CDS; AND HOMEOBOX B6(HOXB6), HOMEOBOX B5 (HOXB5), HOMEOBOX B4 (HOXB4), AND HOMEOBOX B3(HOXB3) GENES, COMPLETE CDS” AF251237 1.55 “HOMO SAPIENS XAGE-1 MRNA,COMPLETE CDS” 1105672.1 1.55 NULL NM_004312 1.55 “HOMO SAPIENS ARRESTIN3, RETINAL (X-ARRESTIN) (ARR3), MRNA” AK056198 1.55 “HOMO SAPIENS CDNAFLJ31636 FIS, CLONE NT2RI2003481” NM_004049 1.55 “HOMO SAPIENSBCL2-RELATED PROTEIN A1 (BCL2A1), MRNA.” NM_003049 1.55 “HOMO SAPIENSSOLUTE CARRIER FAMILY 10 (SODIUM/BILE ACID COTRANSPORTER FAMILY), MEMBER1 (SLC10A1), MRNA.” NM_005122 1.55 “HOMO SAPIENS NUCLEAR RECEPTORSUBFAMILY 1, GROUP I, MEMBER 3 (NR1I3), MRNA” NM_014698 1.55 “HOMOSAPIENS KIAA0792 GENE PRODUCT (KIAA0792), MRNA.” AF168787 1.55 “HOMOSAPIENS VANILLOID RECEPTOR GENE, PARTIAL SEQUENCE; CARKL AND CTNS GENES,COMPLETE CDS; TIP1 GENE, PARTIAL CDS; P2X5B AND P2X5A GENES, COMPLETECDS; AND HUMINAE GENE, PARTIAL CDS” AP000517 1.55 “HOMO SAPIENS GENOMICDNA, CHROMOSOME 6P21.3, HLA CLASS I REGION, SECTION 16/20” NM_0145091.55 “HOMO SAPIENS SERINE HYDROLASE-LIKE (SERHL), MRNA” M96843 1.55“HUMAN STRIATED MUSCLE CONTRACTION REGULATORY PROTEIN (ID2B) MRNA,COMPLETE CDS” NM_003854 1.55 “HOMO SAPIENS INTERLEUKIN 1 RECEPTOR-LIKE 2(IL1RL2), MRNA.” NM_003787 1.55 “HOMO SAPIENS NUCLEOLAR PROTEIN 4(NOL4), MRNA.” NM_005364 1.55 “HOMO SAPIENS MELANOMA ANTIGEN, FAMILY A,8 (MAGEA8), MRNA” NM_021969 1.55 “HOMO SAPIENS NUCLEAR RECEPTORSUBFAMILY 0, GROUP B, MEMBER 2 (NR0B2), MRNA.” Z83075 1.55 “H. SAPIENSFANCONI ANAEMIA GROUP A GENE, EXONS 12, 13 AND 14” NM_000733 1.55 “HOMOSAPIENS CD3E ANTIGEN, EPSILON POLYPEPTIDE (TIT3 COMPLEX) (CD3E), MRNA.”NM_002985 1.55 “HOMO SAPIENS SMALL INDUCIBLE CYTOKINE A5 (RANTES)(SCYA5), MRNA” NM_012306 1.55 “HOMO SAPIENS LIFEGUARD (KIAA0950), MRNA”AF195821 1.55 “HOMO SAPIENS TNG2 (TNG2) MRNA, COMPLETE CDS” NM_0012311.55 “HOMO SAPIENS CALSEQUESTRIN 1 (FAST-TWITCH, SKELETAL MUSCLE)(CASQ1), NUCLEAR GENE ENCODING MITOCHONDRIAL PROTEIN, MRNA.” AJ4145631.55 HOMO SAPIENS CX25 GENE FOR CONNEXIN25 AK074985 1.55 “HOMO SAPIENSCDNA FLJ90504 FIS, CLONE NT2RP3004090, WEAKLY SIMILAR TO GOLIATHPROTEIN” NM_001056 1.54 “HOMO SAPIENS SULFOTRANSFERASE FAMILY,CYTOSOLIC, 1C, MEMBER 1 (SULT1C1), MRNA” NM_001186 1.54 “HOMO SAPIENSBTB AND CNC HOMOLOGY 1, BASIC LEUCINE ZIPPER TRANSCRIPTION FACTOR 1(BACH1), MRNA.” NM_000207 1.54 “HOMO SAPIENS INSULIN (INS), MRNA.”NM_006760 1.54 “HOMO SAPIENS UROPLAKIN 2 (UPK2), MRNA.” T54189 1.54“YA92C11.R1 HOMO SAPIENS CDNA, 5′ END” AK022712 1.54 “HOMO SAPIENS CDNAFLJ12650 FIS, CLONE NT2RM4002054” NM_018249 1.54 “HOMO SAPIENS CDK5REGULATORY SUBUNIT ASSOCIATED PROTEIN 2 (CDK5RAP2), MRNA” NM_015366 1.54“HOMO SAPIENS RHO GTPASE ACTIVATING PROTEIN 8 (ARHGAP8), MRNA.”1452330.5 1.54 NULL L25940 1.54 “HOMO SAPIENS INTEGRAL NUCLEAR ENVELOPEINNER MEMBRANE PROTEIN (LBR) GENE, EXON 11” AA318707 1.54 “HUMAN CYSTICFIBROSIS ANTIGEN MRNA, COMPLETE CDS.” AL137407 1.54 HOMO SAPIENS MRNA;CDNA DKFZP434M232 (FROM CLONE DKFZP434M232) NM_002248 1.54 “HOMO SAPIENSPOTASSIUM INTERMEDIATE/SMALL CONDUCTANCE CALCIUM-ACTIVATED CHANNEL,SUBFAMILY N, MEMBER 1 (KCNN1), MRNA.” NM_005544 1.54 “HOMO SAPIENSINSULIN RECEPTOR SUBSTRATE 1 (IRS1), MRNA.” AF281074 1.54 “HOMO SAPIENSNEUROPILIN 2 (NRP2) GENE, COMPLETE CDS, ALTERNATIVELY SPLICED” AL3599461.54 HOMO SAPIENS MRNA; CDNA DKFZP762G026 (FROM CLONE DKFZP762G026)AL137296 1.54 HOMO SAPIENS MRNA; CDNA DKFZP434M0416 (FROM CLONEDKFZP434M0416) NM_001068 1.54 “HOMO SAPIENS TOPOISOMERASE (DNA) II BETA(180 KD) (TOP2B), MRNA.” NM_014213 1.54 “HOMO SAPIENS HOMEO BOX D9(HOXD9), MRNA.” NM_003392 1.54 “HOMO SAPIENS WINGLESS-TYPE MMTVINTEGRATION SITE FAMILY, MEMBER 5A (WNT5A), MRNA.” AA463818 1.54ZX67D04.R1 HOMO SAPIENS CDNA 5′ END NM_032578 1.54 “HOMO SAPIENSMYOPALLADIN (FLJ14437), MRNA” AL512713 1.54 HOMO SAPIENS MRNA; CDNADKFZP547D086 (FROM CLONE DKFZP547D086) NM_017707 1.54 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ20199 (FLJ20199), MRNA.” NM_014217 1.54 “HOMOSAPIENS POTASSIUM CHANNEL, SUBFAMILY K, MEMBER 2 (KCNK2), MRNA” AK0258141.54 “HOMO SAPIENS CDNA: FLJ22161 FIS, CLONE HRC00290” X69908 1.54 HUMANGENE FOR MITOCHONDRIAL ATP SYNTHASE C SUBUNIT (P2 FORM). AL163300 1.54HOMO SAPIENS CHROMOSOME 21 SEGMENT HS21C100 NM_024895 1.53 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ23209 (FLJ23209), MRNA” NM_058164 1.53 “HOMOSAPIENS OLFACTOMEDIN 2 (OLFM2), MRNA.” AK074293 1.53 “HOMO SAPIENS CDNAFLJ23713 FIS, CLONE HEP12771, HIGHLY SIMILAR TO GRPE PROTEIN HOMOLOG 2PRECURSOR” D50375 1.53 “HOMO SAPIENS MRNA FOR SILENCER ELEMENT, COMPLETECDS” NM_003350 1.53 “HOMO SAPIENS UBIQUITIN-CONJUGATING ENZYME E2VARIANT 2 (UBE2V2), MRNA.” NM_024320 1.53 “HOMO SAPIENS HYPOTHETICALPROTEIN MGC11242 (MGC11242), MRNA” AA873020 1.53 “OA17H03.S1 HOMOSAPIENS CDNA, 3′ END” NM_004385 1.53 “HOMO SAPIENS CHONDROITIN SULFATEPROTEOGLYCAN 2 (VERSICAN) (CSPG2), MRNA.” NM_022127 1.53 “HOMO SAPIENSSOLUTE CARRIER FAMILY 28 (SODIUM-COUPLED NUCLEOSIDE TRANSPORTER), MEMBER3 (SLC28A3), MRNA” NM_000359 1.53 “HOMO SAPIENS TRANSGLUTAMINASE 1 (KPOLYPEPTIDE EPIDERMAL TYPE I,PROTEIN-GLUTAMINE-GAMMA-GLUTAMYLTRANSFERASE) (TGM1), MRNA.” AL1376161.53 HOMO SAPIENS MRNA; CDNA DKFZP434O1311 (FROM CLONE DKFZP434O1311)AA297451 1.53 EST112980 HOMO SAPIENS CDNA 5′ END/CLONE_END = 5′1503632.3 1.53 NULL NM_000387 1.53 “HOMO SAPIENS SOLUTE CARRIER FAMILY25 (CARNITINE/ACYLCARNITINE TRANSLOCASE), MEMBER 20 (SLC25A20),MITOCHONDRIAL PROTEIN ENCODED BY NUCLEAR GENE, MRNA” AF139131 1.53 “HOMOSAPIENS BECLIN 1 (BECN1) MRNA, COMPLETE CDS” NM_080792 1.53 “HOMOSAPIENS BRAIN-IMMUNOGLOBULIN-LIKE MOLECULE WITH TYROSINE-BASEDACTIVATION MOTIFS (BIT), MRNA” M63391 1.53 “HUMAN DESMIN GENE, COMPLETECDS.” D86980 1.52 “HUMAN MRNA FOR KIAA0227 GENE, PARTIAL CDS” NM_1383791.52 “HOMO SAPIENS HYPOTHETICAL PROTEIN BC008988 (LOC91937), MRNA”AF217490 1.52 “HOMO SAPIENS FRAGILE 160 OXIDO REDUCTASE (FOR) GENE,EXONS 8, 9, AND PARTIAL CDS” NM_003629 1.52 “HOMO SAPIENSPHOSPHOINOSITIDE-3-KINASE, REGULATORY SUBUNIT, POLYPEPTIDE 3 (P55,GAMMA) (PIK3R3), MRNA.” NM_052884 1.52 “HOMO SAPIENS SIALIC ACID BINDINGIG-LIKE LECTIN 11 (SIGLEC11), MRNA” AK024406 1.52 “HOMO SAPIENS CDNAFLJ14344 FIS, CLONE THYRO1001142” AL162066 1.52 HOMO SAPIENS MRNA; CDNADKFZP762D096 (FROM CLONE DKFZP762D096); PARTIAL CDS AK055539 1.52 “HOMOSAPIENS CDNA FLJ30977 FIS, CLONE HHDPC2000095, HIGHLY SIMILAR TOCRICETULUS GRISEUS LAYILIN MRNA” NM_015425 1.52 “HOMO SAPIENSDKFZP586M0122 PROTEIN (DKFZP586M0122), MRNA.” NM_032108 1.52 “HOMOSAPIENS SEMA DOMAIN, TRANSMEMBRANE DOMAIN (TM), AND CYTOPLASMIC DOMAIN,(SEMAPHORIN) 6B (SEMA6B), MRNA.” NM_000811 1.52 “HOMO SAPIENSGAMMA-AMINOBUTYRIC ACID (GABA) A RECEPTOR, ALPHA 6 (GABRA6), MRNA”AI718785 1.52 AS58H10.X1 HOMO SAPIENS CDNA 3′ END NM_000748 1.52 “HOMOSAPIENS CHOLINERGIC RECEPTOR, NICOTINIC, BETA POLYPEPTIDE 2 (NEURONAL)(CHRNB2), MRNA” NM_006850 1.52 “HOMO SAPIENS INTERLEUKIN 24 (IL24),MRNA.” J05312 1.52 “HUMAN LIPOPROTEIN ASSOCIATED COAGULATION INHIBITOR(LACI) GENE, EXON 9.” NM_002588 1.52 “HOMO SAPIENS PROTOCADHERIN GAMMASUBFAMILY C, 3 (PCDHGC3), TRANSCRIPT VARIANT 1, MRNA” NM_031929 1.52“HOMO SAPIENS TESTIS-SPECIFIC TRANSCRIPT, Y-LINKED 11 (TTTY11), MRNA”AI038940 1.52 “OY86E05.X1 HOMO SAPIENS CDNA, 3′ END” NM_003482 1.52“HOMO SAPIENS MYELOID/LYMPHOID OR MIXED-LINEAGE LEUKEMIA 2 (MLL2), MRNA”U66047 1.52 HOMO SAPIENS CLONE Z′3-1 PLACENTA EXPRESSED MRNA FROMCHROMOSOME X NM_014909 1.52 “HOMO SAPIENS KIAA1036 PROTEIN (KIAA1036),MRNA.” AA873769 1.52 “OI06F02.S1 NCI_CGAP_GC4 HOMO SAPIENS CDNA CLONEIMAGE: 1475739 3′, MRNA SEQUENCE” AA037140 1.52 “ZC53F10.R1 HOMO SAPIENSCDNA, 5′ END” NM_006365 1.52 “HOMO SAPIENS TRANSCRIPTIONAL ACTIVATOR OFTHE C-FOS PROMOTER (CROC4), MRNA” NM_003803 1.52 “HOMO SAPIENS MYOMESIN1 (SKELEMIN) (185 KD) (MYOM1), MRNA.” AB023151 1.52 “HOMO SAPIENS MRNAFOR KIAA0934 PROTEIN, PARTIAL CDS”. NM_006662 1.52 “HOMO SAPIENSSNF2-RELATED CBP ACTIVATOR PROTEIN (SRCAP), MRNA.” NM_032369 1.52 “HOMOSAPIENS HYPOTHETICAL PROTEIN MGC15619 (MGC15619), MRNA” AL163259 1.52NULL NM_000836 1.52 “HOMO SAPIENS GLUTAMATE RECEPTOR, IONOTROPIC,N-METHYL D- ASPARTATE 2D (GRIN2D), MRNA” M10014 1.51 HUMAN FIBRINOGENGENE (FGG). NM_017618 1.51 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ20006(FLJ20006), MRNA” AB009076 1.51 “HOMO SAPIENS GENE FOR COMPLEMENT C1S,PARTIAL CDS” AF118081 1.51 “HOMO SAPIENS PRO1900 MRNA, COMPLETE CDS”NM_004694 1.51 “HOMO SAPIENS SOLUTE CARRIER FAMILY 16 (MONOCARBOXYLICACID TRANSPORTERS), MEMBER 6 (SLC16A6), MRNA.” AI052482 1.51 “OZ19F08.X1HOMO SAPIENS CDNA, 3′ END” 887776.1 1.51 “PROTEIN WITH VERY STRONGSIMILARITY TO ALBUMIN (RAT ALB), WHICH IS A BLOOD PLASMA PROTEIN, HUMANALB IS ASSOCIATED WITH FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA ANDANALBUMINEMIA, MEMBER OF THE SERUM ALBUMIN FAMILY” AF313465 1.51 “HOMOSAPIENS SODIUM BICARBONATE COTRANSPORTER (SLC4A9) MRNA, PARTIAL CDS”M17285 1.51 HUMAN INSULIN-LIKE GROWTH FACTOR (IGF-II) GENE M87708 1.51HUMAN SIMPLE REPEAT POLYMORPHISM NM_080739 1.51 “HOMO SAPIENS CHROMOSOME20 OPEN READING FRAME 141 (C20ORF141), MRNA.” NM_032621 1.51 “HOMOSAPIENS X-LINKED PROTEIN (DJ79P11.1), MRNA.” NM_005425 1.51 “HOMOSAPIENS TRANSITION PROTEIN 2 (DURING HISTONE TO PROTAMINE REPLACEMENT)(TNP2), MRNA.” NM_007017 1.51 “HOMO SAPIENS SRY (SEX DETERMINING REGIONY)-BOX 30 (SOX30), MRNA.” NM_000340 1.51 “HOMO SAPIENS SOLUTE CARRIERFAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 2 (SLC2A2), MRNA.”NM_018652 1.51 “HOMO SAPIENS GOLGIN-LIKE PROTEIN (GLP), MRNA” NM_0312751.51 “HOMO SAPIENS TESTIS EXPRESSED SEQUENCE 12 (TEX12), MRNA” NM_0026501.51 “HOMO SAPIENS PHOSPHATIDYLINOSITOL 4-KINASE, CATALYTIC, ALPHAPOLYPEPTIDE (PIK4CA), TRANSCRIPT VARIANT 1, MRNA.” NM_006258 1.51 “HOMOSAPIENS PROTEIN KINASE, CGMP-DEPENDENT, TYPE I (PRKG1), MRNA.” AB0206711.51 “HOMO SAPIENS MRNA FOR KIAA0864 PROTEIN, PARTIAL CDS” NM_0247871.51 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ12526 (FLJ12526), MRNA”AF055378 1.51 “HOMO SAPIENS LONG FORM TRANSCRIPTION FACTOR C-MAF (C-MAF)GENE, EXON 2 AND PARTIAL CDS” BC001427 1.51 “HOMO SAPIENS, HYPOTHETICALPROTEIN FLJ11320, CLONE MGC: 894 IMAGE: 3139599, MRNA, COMPLETE CDS”NM_022803 1.51 “HOMO SAPIENS UNCOUPLING PROTEIN 3 (MITOCHONDRIAL, PROTONCARRIER) (UCP3), TRANSCRIPT VARIANT SHORT, NUCLEAR GENE ENCODINGMITOCHONDRIAL PROTEIN, MRNA.” NM_016944 1.51 “HOMO SAPIENS TASTERECEPTOR, TYPE 2, MEMBER 4 (TAS2R4), MRNA” L44140 1.51 “HUMAN CHROMOSOMEX REGION FROM FILAMIN (FLN) GENE TO GLUCOSE-6-PHOSPHATE DEHYDROGENASE(G6PD) GENE, COMPLETE CDS'S.” AB046814 1.51 “HOMO SAPIENS MRNA FORKIAA1594 PROTEIN, PARTIAL CDS” AK000694 1.50 “HOMO SAPIENS CDNA FLJ20687FIS, CLONE KAIA302, HIGHLY SIMILAR TO AF039702 HOMO SAPIENS ANTIGENNY-CO-43 MRNA” AK024999 1.50 “HOMO SAPIENS CDNA: FLJ21346 FIS, CLONECOL02705” NM_003212 1.50 “HOMO SAPIENS TERATOCARCINOMA-DERIVED GROWTHFACTOR 1 (TDGF1), MRNA” NM_014634 1.50 “HOMO SAPIENS KIAA0015 GENEPRODUCT (KIAA0015), MRNA.” AP000497 1.50 “HOMO SAPIENS GENOMIC DNA,CHROMOSOME 3P21.3, CLONE: 301 TO 308, ANTI-ONCOGENE REGION, SECTION 5/5”NM_020482 1.50 “HOMO SAPIENS ACTIVATOR OF CAMP-RESPONSIVE ELEMENTMODULATOR (CREM) IN TESTIS (ACT), MRNA” NM_001330 1.50 “HOMO SAPIENSCARDIOTROPHIN 1 (CTF1), MRNA.” NM_005275 1.50 “HOMO SAPIENS GUANINENUCLEOTIDE BINDING PROTEIN-LIKE 1 (GNL1), MRNA”

APPENDIX 2

Down Regulated Genes with Treatment Fex: Accession Fold Change Number(Fex/DMSO) Gene Description NM_006984 0.13 “HOMO SAPIENS CLAUDIN 10(CLDN10), MRNA” NM_000710 0.17 “HOMO SAPIENS BRADYKININ RECEPTOR B1(BDKRB1), MRNA” NM_031958 0.20 “HOMO SAPIENS KERATIN ASSOCIATED PROTEIN3.1 (KRTAP3.1), MRNA” 475365.6 0.21 “MEMBER OF THE CARBOXYPEPTIDASE AMETALLOPROTEASE (M14) FAMILY OF ZINC CARBOXYPEPTIDASES, HAS MODERATESIMILARITY TO CARBOXYPEPTIDASE B2 (MOUSE CPB2), WHICH IS A PLASMAPRO-FORM METALLOPROTEASE THAT IS AN ACUTE PHASE PROTEIN UPREGULATED ININFLAMMATION” AK026959 0.23 “HOMO SAPIENS CDNA: FLJ23306 FIS, CLONEHEP11541” NM_030572 0.23 “HOMO SAPIENS HYPOTHETICAL PROTEIN MGC10946(MGC10946), MRNA” NM_004407 0.24 “HOMO SAPIENS DENTIN MATRIX ACIDICPHOSPHOPROTEIN (DMP1), MRNA” NM_018436 0.25 “HOMO SAPIENS ALLANTOICASE(ALLC), MRNA” NM_003102 0.26 “HOMO SAPIENS SUPEROXIDE DISMUTASE 3,EXTRACELLULAR (SOD3), MRNA” NM_004575 0.26 “HOMO SAPIENS POU DOMAIN,CLASS 4, TRANSCRIPTION FACTOR 2 (POU4F2), MRNA” D28113 0.26 “HUMAN MRNAFOR MOBP (MYELIN-ASSOCIATED OLIGODENDROCYTIC BASIC PROTEIN), COMPLETECDS, CLONE HOPRP1” NM_144658 0.28 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ32122 (FLJ32122), MRNA” NM_000584 0.29 “HOMO SAPIENS INTERLEUKIN 8(IL8), MRNA.” NM_024687 0.30 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ23049(FLJ23049), MRNA” NM_014391 0.31 “HOMO SAPIENS CARDIAC ANKYRIN REPEATPROTEIN (CARP), MRNA” Z60717 0.31 “H. SAPIENS CPG ISLAND DNA GENOMICMSE1 FRAGMENT, CLONE 33A10, FORWARD READ CPG33A10.FT1|” NM_024340 0.32“HOMO SAPIENS HYPOTHETICAL PROTEIN MGC4179 (MGC4179), MRNA” D86425 0.32“HOMO SAPIENS MRNA FOR OSTEONIDOGEN, COMPLETE CDS” AL122109 0.33 HOMOSAPIENS MRNA; CDNA DKFZP434M1827 (FROM CLONE DKFZP434M1827) NM_0243060.33 “HOMO SAPIENS FATTY ACID HYDROXYLASE (FAAH), MRNA” AF043195 0.34“HOMO SAPIENS TIGHT JUNCTION PROTEIN ZO-2 (TJP2) GENE, ALTERNATIVEPROMOTER PA AND EXON A” NM_002089 0.35 “HOMO SAPIENS GRO2 ONCOGENE(GRO2), MRNA.” NM_018679 0.35 “HOMO SAPIENS T-COMPLEX 11 (MOUSE)(TCP11), MRNA” NM_003311 0.35 “HOMO SAPIENS TUMOR SUPPRESSINGSUBTRANSFERABLE CANDIDATE 3 (TSSC3), MRNA.” NM_014890 0.36 “HOMO SAPIENSDOWNREGULATED IN OVARIAN CANCER 1 (DOC1), MRNA.” NM_032883 0.36 “HOMOSAPIENS CHROMOSOME 20 OPEN READING FRAME 100 (C20ORF100), MRNA”NM_005925 0.36 “HOMO SAPIENS MEPRIN A, BETA (MEP1B), MRNA” BC000623 0.37“HOMO SAPIENS, SIMILAR TO HYPOTHETICAL PROTEIN FLJ20211, CLONE MGC: 1068IMAGE: 3346325, MRNA, COMPLETE CDS” 180648.1 0.37 PROTEIN CONTAININGFIVE MORN (MEMBRANE OCCUPATION AND RECOGNITION NEXUS) REPEATS NM_0322630.38 “HOMO SAPIENS HYPOTHETICAL PROTEIN DKFZP434B227 (DKFZP434B227),MRNA” AK023937 0.38 “HOMO SAPIENS CDNA FLJ13875 FIS, CLONE THYRO1001374,WEAKLY SIMILAR TO CYTOSOLIC ACYL COENZYME A THIOESTER HYDROLASE (EC3.1.2.2)” AK026071 0.38 “HOMO SAPIENS CDNA: FLJ22418 FIS, CLONEHRC08590” D55641 0.39 “HUMAN SKIN FIBROBLAST PABL (PSEUDOAUTOSOMALBOUNDARY-LIKE SEQUENCE) MRNA, CLONE SK13” BF692587 0.39 602248939F1 HOMOSAPIENS CDNA 5′ END AF168681 0.39 “HOMO SAPIENS CRIM1 PROTEIN GENE,PARTIAL CDS; AND FEZ2 GENE, PARTIAL SEQUENCE” AL046937 0.40DKFZP586I2417_R1 HOMO SAPIENS CDNA 5′ END NM_014331 0.40 “HOMO SAPIENSSOLUTE CARRIER FAMILY 7, (CATIONIC AMINO ACID TRANSPORTER, Y+ SYSTEM)MEMBER 11 (SLC7A11), MRNA” NM_012275 0.41 “HOMO SAPIENS INTERLEUKIN 1FAMILY, MEMBERS (DELTA) (IL1F5), MRNA” NM_015003 0.42 “HOMO SAPIENSGOLGIN-67 (KIAA0855), MRNA” U09197 0.42 HUMAN 5.5 KB MRNA UPREGULATED INRETINOIC ACID TREATED HL-60 NEUTROPHILIC CELLS AL137477 0.42 HOMOSAPIENS MRNA; CDNA DKFZP434K2323 (FROM CLONE DKFZP434K2323); PARTIAL CDSNM_006516 0.42 “HOMO SAPIENS SOLUTE CARRIER FAMILY 2 (FACILITATEDGLUCOSE TRANSPORTER), MEMBER 1 (SLC2A1), MRNA.” AI435998 0.42“TH80E05.X1 HOMO SAPIENS CDNA, 3′ END” AL050169 0.42 HOMO SAPIENS MRNA;CDNA DKFZP586D0922 (FROM CLONE DKFZP586D0922) NM_006279 0.42 “HOMOSAPIENS SIALYLTRANSFERASE 6 (N-ACETYLLACOSAMINIDE ALPHA 2,3-SIALYLTRANSFERASE) (SIAT6), MRNA.” NM_006163 0.42 “HOMO SAPIENS NUCLEARFACTOR (ERYTHROID-DERIVED 2), 45 KD (NFE2), MRNA.” BC035810 0.43 “HOMOSAPIENS, CLONE IMAGE: 5754421, MRNA, PARTIAL CDS” AK026485 0.43 “HOMOSAPIENS CDNA: FLJ22832 FIS, CLONE KAIA4195” NM_017911 0.43 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ20635 (FLJ20635), MRNA” L40326 0.43 “HOMOSAPIENS HEPATITIS B VIRUS X-ASSOCIATED PROTEIN 1 MRNA, COMPLETE CDS”AK000819 0.44 “HOMO SAPIENS CDNA FLJ20812 FIS, CLONE ADSE01316”NM_002423 0.44 “HOMO SAPIENS MATRIX METALLOPROTEINASE 7 (MATRILYSIN,UTERINE) (MMP7), MRNA.” AK097430 0.44 “HOMO SAPIENS CDNA FLJ40111 FIS,CLONE TESTI2008320, MODERATELY SIMILAR TO HOMO SAPIENS MITOGEN-ACTIVATEDPROTEIN KINASE PHOSPHATASE X (MKPX) MRNA” NM_015515 0.45 “HOMO SAPIENSTYPE I INTERMEDIATE FILAMENT CYTOKERATIN (HAIK1), MRNA.” NM_139215 0.45“HOMO SAPIENS TAF15 RNA POLYMERASE II, TATA BOX BINDING PROTEIN(TBP)-ASSOCIATED FACTOR, 68 KD (TAF15), TRANSCRIPT VARIANT 1, MRNA”NM_003025 0.45 “HOMO SAPIENS SH3-DOMAIN GRB2-LIKE 1 (SH3GL1), MRNA.”BC007008 0.45 “HOMO SAPIENS, CRYSTALLIN, ALPHA B, CLONE MGC: 12326IMAGE: 3933748, MRNA, COMPLETE CDS” NM_005195 0.46 “HOMO SAPIENSCCAAT/ENHANCER BINDING PROTEIN (C/EBP), DELTA (CEBPD), MRNA.” NM_0045910.46 “HOMO SAPIENS SMALL INDUCIBLE CYTOKINE SUBFAMILY A (CYS-CYS),MEMBER 20 (SCYA20), MRNA” AK024998 0.46 “HOMO SAPIENS CDNA: FLJ21345FIS, CLONE COL02694” NM_017773 0.47 “HUMAN DEFENSIN 6 MRNA, COMPLETECDS.” AP000505 0.47 “HOMO SAPIENS GENOMIC DNA, CHROMOSOME 6P21.3, HLACLASS I REGION, SECTION 4/20” NM_012206 0.47 “HOMO SAPIENS HEPATITIS AVIRUS CELLULAR RECEPTOR 1 (HAVCR-1), MRNA.” NM_016218 0.47 “HOMO SAPIENSPOLYMERASE (DNA-DIRECTED) KAPPA (POLK), MRNA” NM_021634 0.47 “HOMOSAPIENS LEUCINE-RICH REPEAT-CONTAINING G PROTEIN-COUPLED RECEPTOR 7(LGR7), MRNA” AB032969 0.47 “HOMO SAPIENS MRNA FOR KIAA1143 PROTEIN,PARTIAL CDS” NM_005354 0.47 “HOMO SAPIENS JUN D PROTO-ONCOGENE (JUND),MRNA.” NM_001554 0.48 “HOMO SAPIENS CYSTEINE-RICH, ANGIOGENIC INDUCER,61 (CYR61), MRNA” NM_000928 0.48 “HOMO SAPIENS PHOSPHOLIPASE A2, GROUPIB (PANCREAS) (PLA2G1B), NUCLEAR GENE ENCODING MITOCHONDRIAL PROTEIN,MRNA” NM_017736 0.48 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ20274(FLJ20274), MRNA” M37457 0.48 “HUMAN NA+, K+ -ATPASE CATALYTIC SUBUNITALPHA-III ISOFORM GENE, EXON 23, CLONE LAMBDA-NK-ALPHA-R3-2” NM_0005300.49 “HOMO SAPIENS MYELIN PROTEIN ZERO (CHARCOT-MARIE-TOOTH NEUROPATHY1B) (MPZ), MRNA” D43639 0.49 “HUMAN GENE FOR PREPROADRENOMEDULLIN,COMPLETE CDS (EXON 1-4)” NM_005420 0.49 “HOMO SAPIENS SULFOTRANSFERASE,ESTROGEN-PREFERRING (STE), MRNA.” NM_032837 0.49 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ14775 (FLJ14775), MRNA” 203751.1 0.49 PROTEIN OFUNKNOWN FUNCTION NM_021101 0.49 “HOMO SAPIENS CLAUDIN 1 (CLDN1), MRNA.”NM_024889 0.49 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ23537 (FLJ23537),MRNA” NM_022133 0.49 “HOMO SAPIENS SORTING NEXIN 16 (SNX16), MRNA”AB011128 0.49 “HOMO SAPIENS MRNA FOR KIAA0556 PROTEIN, PARTIAL CDS”AK090409 0.49 HOMO SAPIENS MRNA FOR FLJ00300 PROTEIN NM_022122 0.49“HOMO SAPIENS MATRIX METALLOPROTEINASE 27 (MMP27), MRNA” NM_001300 0.50“HOMO SAPIENS CORE PROMOTER ELEMENT BINDING PROTEIN (COPEB), MRNA”NM_003557 0.50 “HOMO SAPIENS PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE,TYPE I, ALPHA (PIP5K1A), MRNA.” AB037779 0.50 “HOMO SAPIENS MRNA FORKIAA1358 PROTEIN, PARTIAL CDS” NM_004420 0.50 “HOMO SAPIENS DUALSPECIFICITY PHOSPHATASE 8 (DUSP8), MRNA.” NM_005627 0.50 “HOMO SAPIENSSERUM/GLUCOCORTICOID REGULATED KINASE (SGK), MRNA.” 1168293.1 0.50 NULLAB007892 0.50 “HOMO SAPIENS KIAA0432 MRNA, COMPLETE CDS” NM_016140 0.50“HOMO SAPIENS BRAIN SPECIFIC PROTEIN (LOC51673), MRNA.” NM_012342 0.50“HOMO SAPIENS PUTATIVE TRANSMEMBRANE PROTEIN (NMA), MRNA.” NM_0010860.50 “HOMO SAPIENS ARYLACETAMIDE DEACETYLASE (ESTERASE) (AADAC), MRNA.”1345454.1 0.50 NULL NM_033344 0.50 “HOMO SAPIENS EGL NINE HOMOLOG 3 (C.ELEGANS) (EGLN3), MRNA.” NM_003113 0.51 “HOMO SAPIENS NUCLEAR ANTIGENSP100 (SP100), MRNA” BC015134 0.51 “HOMO SAPIENS, CLONE IMAGE: 3934391,MRNA” NM_002260 0.51 “HOMO SAPIENS KILLER CELL LECTIN-LIKE RECEPTORSUBFAMILY C, MEMBER 2 (KLRC2), MRNA.” AK097698 0.51 “HOMO SAPIENS CDNAFLJ40379 FIS, CLONE TESTI2035262, WEAKLY SIMILAR TO PROACTIVATORPOLYPEPTIDE PRECURSOR” BC004982 0.51 “HOMO SAPIENS, GLUCOSE PHOSPHATEISOMERASE, CLONE MGC: 3935 IMAGE: 2906270, MRNA, COMPLETE CDS” NM_0016290.51 “HOMO SAPIENS ARACHIDONATE 5-LIPOXYGENASE-ACTIVATING PROTEIN(ALOX5AP), MRNA.” NM_023068 0.51 “HOMO SAPIENS SIALOADHESIN (SN), MRNA.”NM_005978 0.52 “HOMO SAPIENS S100 CALCIUM BINDING PROTEIN A2 (S100A2),MRNA.” Z72499 0.52 H. SAPIENS MRNA FOR HERPESVIRUS ASSOCIATEDUBIQUITIN-SPECIFIC PROTEASE (HAUSP) AP003355 0.52 “HOMO SAPIENS GENOMICDNA, CHROMOSOME 8Q23, CLONE: KB1517D11” NM_033260 0.52 “HOMO SAPIENSWINGED HELIX/FORKHEAD TRANSCRIPTION FACTOR (HFH1), MRNA” NM_001901 0.52“HOMO SAPIENS CONNECTIVE TISSUE GROWTH FACTOR (CTGF), MRNA.” NM_0015620.52 “HOMO SAPIENS INTERLEUKIN 18 (INTERFERON-GAMMA-INDUCING FACTOR)(IL18), MRNA.” 1401176.1 0.52 NULL AJ420585 0.52 HOMO SAPIENS MRNA FULLLENGTH INSERT CDNA CLONE EUROIMAGE 1964662 BG752423 0.52 “602730910F1NIH_MGC_43 HOMO SAPIENS CDNA CLONE IMAGE: 4874427 5′, MRNA SEQUENCE”BC008810 0.52 “HOMO SAPIENS, CLONE IMAGE: 3948909, MRNA, PARTIAL CDS”NM_020299 0.52 “HOMO SAPIENS ALDO-KETO REDUCTASE FAMILY 1, MEMBER B10(ALDOSE REDUCTASE) (AKR1B10), MRNA.” NM_003358 0.52 “HOMO SAPIENSUDP-GLUCOSE CERAMIDE GLUCOSYLTRANSFERASE (UGCG), MRNA.” M80478 0.52“HUMAN PLATELET GLYCOPROTEIN IX PRECURSOR (GPIX) GENE, COMPLETE CDS”NM_001657 0.53 “HOMO SAPIENS AMPHIREGULIN (SCHWANNOMA-DERIVED GROWTHFACTOR) (AREG), MRNA.” NM_003212 0.53 “HOMO SAPIENSTERATOCARCINOMA-DERIVED GROWTH FACTOR 1 (TDGF1), MRNA.” NM_024325 0.53“HOMO SAPIENS HYPOTHETICAL PROTEIN MGC10715 (MGC10715), MRNA” NM_0052420.53 “HOMO SAPIENS COAGULATION FACTOR II (THROMBIN) RECEPTOR-LIKE 1(F2RL1), MRNA” NM_005797 0.53 “HOMO SAPIENS EPITHELIAL V-LIKE ANTIGEN 1(EVA1), MRNA.” NM_001348 0.53 “HOMO SAPIENS DEATH-ASSOCIATED PROTEINKINASE 3 DAPK3, MRNA.” NM_024501 0.53 “HOMO SAPIENS HOMEO BOX D1(HOXD1), MRNA” NM_004864 0.53 “HOMO SAPIENS PROSTATE DIFFERENTIATIONFACTOR (PLAB), MRNA” AF016903 0.53 “HOMO SAPIENS AGRIN PRECURSOR MRNA,PARTIAL CDS” NM_152908 0.53 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ31196(FLJ31196), MRNA” NM_006753 0.54 “HOMO SAPIENS SURFEIT 6 (SURF6), MRNA”NM_017654 0.54 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ20073 (FLJ20073),MRNA” NM_001165 0.54 “HOMO SAPIENS BACULOVIRAL IAP REPEAT-CONTAINING 3(BIRC3), MRNA.” NM_016639 0.54 “HOMO SAPIENS TYPE I TRANSMEMBRANEPROTEIN FN14 (FN14), MRNA.” AL162045 0.54 HOMO SAPIENS MRNA; CDNADKFZP761P0212 (FROM CLONE DKFZP761P0212); PARTIAL CDS AK026784 0.54“HOMO SAPIENS CDNA: FLJ23131 FIS, CLONE LNG08502” NM_145298 0.54 “HOMOSAPIENS SIMILAR TO PHORBOLIN 3 (APOBEC1-LIKE) (LOC200316), MRNA”BG546997 0.54 602573989F1 HOMO SAPIENS CDNA 5′ END NM_017651 0.54 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ20069 (FLJ20069), MRNA” NM_001346 0.54“HOMO SAPIENS DIACYLGLYCEROL KINASE, GAMMA (90 KD) (DGKG), MRNA.”NM_030587 0.54 “HOMO SAPIENS UDP-GAL: BETAGLCNAC BETA 1,4-GALACTOSYLTRANSFERASE, POLYPEPTIDE 2 (B4GALT2), TRANSCRIPT VARIANT 1,MRNA.” NM_024796 0.54 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ22639(FLJ22639), MRNA” NM_015720 0.54 “HOMO SAPIENS ENDOGLYCAN (PODLX2),MRNA.” AK023317 0.54 “HOMO SAPIENS CDNA FLJ13255 FIS, CLONEOVARC1000800, MODERATELY SIMILAR TO MITOCHONDRIAL STRESS-70 PROTEINPRECURSOR” NM_006901 0.54 “HOMO SAPIENS MYOSIN IXA (MYO9A), MRNA.”NM_001553 0.55 “HOMO SAPIENS INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN7 (IGFBP7), MRNA” M80899 0.55 “HUMAN NOVEL PROTEIN AHNAK MRNA, PARTIALSEQUENCE” NM_002658 0.55 “HOMO SAPIENS PLASMINOGEN ACTIVATOR, UROKINASE(PLAU), MRNA.” NM_012227 0.55 “HOMO SAPIENS PSEUDOAUTOSOMAL GTP-BINDINGPROTEIN-LIKE (PGPL), MRNA.” NM_022783 0.55 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ12428 (FLJ12428), MRNA.” AK024489 0.55 “HOMO SAPIENS MRNA FORFLJ00089 PROTEIN, PARTIAL CDS” NM_002228 0.55 “HOMO SAPIENS V-JUNSARCOMA VIRUS 17 ONCOGENE HOMOLOG (AVIAN) (JUN), MRNA.” NM_000683 0.55“HOMO SAPIENS ADRENERGIC, ALPHA-2C-, RECEPTOR (ADRA2C), MRNA.” AL1366800.55 HOMO SAPIENS MRNA; CDNA DKFZP564C2478 (FROM CLONE DKFZP564C2478);COMPLETE CDS NM_006931 0.55 “HOMO SAPIENS SOLUTE CARRIER FAMILY 2(FACILITATED GLUCOSE TRANSPORTER), MEMBER 3 (SLC2A3), MRNA.” NM_0190960.55 “HOMO SAPIENS GTP BINDING PROTEIN 2 (GTPBP2), MRNA.” AF218032 0.55HOMO SAPIENS CLONE PP902 UNKNOWN MRNA NM_002648 0.55 “HOMO SAPIENS PIM-1ONCOGENE (PIM1), MRNA.” NM_002892 0.55 “HOMO SAPIENS RETINOBLASTOMABINDING PROTEIN 1 (RBBP1), TRANSCRIPT VARIANT 1, MRNA” NM_032119 0.55“HOMO SAPIENS VERY LARGE G PROTEIN-COUPLED RECEPTOR 1 (VLGR1), MRNA”NM_024606 0.55 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ11756 (FLJ11756),MRNA.” NM_003082 0.56 “HOMO SAPIENS SMALL NUCLEAR RNA ACTIVATINGCOMPLEX, POLYPEPTIDE 1, 43 KD (SNAPC1), MRNA.” NM_022837 0.56 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ22833 (FLJ22833), MRNA” NM_025043 0.56“HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ22404 (FLJ22404), MRNA” NM_0044680.56 “HOMO SAPIENS FOUR AND A HALF LIM DOMAINS 3 (FHL3), MRNA.” L193140.56 “HUMAN HRY GENE, COMPLETE CDS” AL119114 0.56 “DKFZP761H1212_S1 HOMOSAPIENS CDNA, 3′ END” NM_001453 0.56 “HOMO SAPIENS FORKHEAD BOX C1(FOXC1), MRNA” NM_000354 0.56 “HOMO SAPIENS SERINE (OR CYSTEINE)PROTEINASE INHIBITOR, CLADE A (ALPHA-1 ANTIPROTEINASE, ANTITRYPSIN),MEMBER 7 (SERPINA7), MRNA” X03069 0.56 HUMAN MRNA FOR HLA-D CLASS IIANTIGEN DR1 BETA CHAIN NM_152901 0.56 “HOMO SAPIENS PYRIN-DOMAINCONTAINING PROTEIN 1 (PYC1), MRNA” NM_012242 0.56 “HOMO SAPIENS DICKKOPFHOMOLOG 1 (XENOPUS LAEVIS) (DKK1), MRNA.” NM_033445 0.56 “HOMO SAPIENSSIMILAR TO H2A HISTONE FAMILY, MEMBER A (H. SAPIENS) (MGC3165), MRNA”X70287 0.56 “H. SAPIENS GENE FOR THIOREDOXIN, EXONS 2 AND 3” NM_0181770.56 “HOMO SAPIENS NEDD4 BINDING PROTEIN 2 (N4BP2), MRNA” AL390142 0.56HOMO SAPIENS MRNA; CDNA DKFZP547N024 (FROM CLONE DKFZP547N024) AB0386890.56 “HOMO SAPIENS AHSG GENE FOR ALPHA2-HS GLYCOPROTEIN, COMPLETE CDS”NM_017876 0.56 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ20552 (FLJ20552),MRNA.” AL834442 0.56 HOMO SAPIENS MRNA; CDNA DKFZP761B2210 (FROM CLONEDKFZP761B2210) NG_001068 0.56 “HOMO SAPIENS ACTIN, GAMMA PSEUDOGENE 1(ACTGP1) ON CHROMOSOME 3” NM_012267 0.56 “HOMO SAPIENS HSP70-INTERACTINGPROTEIN (HSPBP1), MRNA.” NM_024114 0.57 “HOMO SAPIENS HYPOTHETICALPROTEIN MGC4827 (MGC4827), MRNA” NM_000337 0.57 “HOMO SAPIENSSARCOGLYCAN, DELTA (35 KD DYSTROPHIN-ASSOCIATED GLYCOPROTEIN) (SGCD),MRNA” NM_018929 0.57 “HOMO SAPIENS PROTOCADHERIN GAMMA SUBFAMILY C, 5(PCDHGC5), TRANSCRIPT VARIANT 1, MRNA” NM_015363 0.57 “HOMO SAPIENS ZINCFINGER, IMPRINTED 2 (ZIM2), MRNA” NM_004064 0.57 “HOMO SAPIENSCYCLIN-DEPENDENT KINASE INHIBITOR 1B (P27, KIP1) (CDKN1B), MRNA”NM_015894 0.57 “HOMO SAPIENS STATHMIN-LIKE 3 (STMN3), MRNA.” NM_0148100.57 “HOMO SAPIENS KIAA0480 GENE PRODUCT (KIAA0480), MRNA.” NM_0050350.57 “HOMO SAPIENS POLYMERASE (RNA) MITOCHONDRIAL (DNA DIRECTED)(POLRMT), NUCLEAR GENE ENCODING MITOCHONDRIAL PROTEIN, MRNA” 475198.10.57 “PROTEIN WITH HIGH SIMILARITY TO RAT RINZF, WHICH BINDS A RAT GASREGULATORY ELEMENT IMPORTANT FOR PANCREAS INSULINOMA-SPECIFICEXPRESSION, CONTAINS TWO C2H2 TYPE ZINC FINGER DOMAINS AND A BTB (BR-C,TTK AND BABOR) OR POZ (POX VIRUS AND ZINC FINGER) DOMAI NM_017958 0.57“HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ20783 (FLJ20783), MRNA.” AB0514920.57 “HOMO SAPIENS MRNA FOR KIAA1705 PROTEIN, PARTIAL CDS” NM_0326240.57 “HOMO SAPIENS HYPOTHETICAL BRAIN PROTEIN MY050 (MY050), MRNA”NM_002307 0.57 “HOMO SAPIENS LECTIN, GALACTOSIDE-BINDING, SOLUBLE, 7(GALECTIN 7) (LGALS7), MRNA.” NM_002333 0.57 “HOMO SAPIENS LOW DENSITYLIPOPROTEIN RECEPTOR-RELATED PROTEIN 3 (LRP3), MRNA.” AK027843 0.57“HOMO SAPIENS CDNA FLJ14937 FIS, CLONE PLACE1010231, WEAKLY SIMILAR TOCELL SURFACE GLYCOPROTEIN EMR1 PRECURSOR” NM_006623 0.57 “HOMO SAPIENSPHOSPHOGLYCERATE DEHYDROGENASE (PHGDH), MRNA” NM_024765 0.57 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ12401 (FLJ12401), MRNA” AF181897 0.58“HOMO SAPIENS WRN (WRN) GENE, COMPLETE CDS” 1330303.1 0.58 NULLNM_139314 0.58 “HOMO SAPIENS ANGIOPOIETIN-LIKE 4 (ANGPTL4), TRANSCRIPTVARIANT 1, MRNA” M25295 0.58 “HUMAN KERATINOCYTE GROWTH FACTOR MRNA,COMPLETE CDS” NM_001550 0.58 “HOMO SAPIENS INTERFERON-RELATEDDEVELOPMENTAL REGULATOR 1 (IFRD1), MRNA” NM_014059 0.58 “HOMO SAPIENSRGC32 PROTEIN (RGC32), MRNA” NM_018017 0.58 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ10188 (FLJ10188), MRNA.” NM_020130 0.58 “HOMO SAPIENSCHROMOSOME 8 OPEN READING FRAME 4 (C8ORF4), MRNA” NM_002856 0.58 “HOMOSAPIENS POLIOVIRUS RECEPTOR-RELATED 2 (HERPESVIRUS ENTRY MEDIATOR B)(PVRL2), MRNA.” J02853 0.58 “HOMO SAPIENS CASEIN KINASE II ALPHA SUBUNITMRNA, COMPLETE CDS” NM_018364 0.58 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ11220 (FLJ11220), MRNA” NM_000670 0.58 “HOMO SAPIENS ALCOHOLDEHYDROGENASE 4 (CLASS II), PI POLYPEPTIDE (ADH4), MRNA.” AK095284 0.58“HOMO SAPIENS CDNA FLJ37965 FIS, CLONE CTONG2009844” U65404 0.58 “HUMANERYTHROID-SPECIFIC TRANSCRIPTION FACTOR EKLF MRNA, COMPLETE CDS”NM_004269 0.58 “HOMO SAPIENS COFACTOR REQUIRED FOR SP1 TRANSCRIPTIONALACTIVATION, SUBUNIT 8 (34 KD) (CRSP8), MRNA.” NM_018231 0.58 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ10815 (FLJ10815), MRNA.” AF070443 0.58“HOMO SAPIENS GLCNAC-1-P TRANSFERASE GENE, EXONS 5 THROUGH 9 ANDCOMPLETE CDS” NM_024679 0.58 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ11939(FLJ11939), MRNA” NM_000422 0.58 “HOMO SAPIENS KERATIN 17 (KRT17), MRNA”AF274889 0.58 “HOMO SAPIENS GLUCOSE TRANSPORTER 3 GENE, EXONS 1 TO 6”NM_052830 0.58 “HOMO SAPIENS GAMMA-GLUTAMYLTRANSFERASE-LIKE 3 (GGTL3),MRNA” 1330160.23 0.58 PROTEIN OF UNKNOWN FUNCTION 403813.2 0.58 PROTEINOF UNKNOWN FUNCTION NM_020921 0.58 “HOMO SAPIENS NINEIN (GSK3BINTERACTING PROTEIN) (NIN), MRNA” NM_024067 0.58 “HOMO SAPIENSHYPOTHETICAL PROTEIN MGC2718 (MGC2718), MRNA” NM_016210 0.59 “HOMOSAPIENS G20 PROTEIN (LOC51161), MRNA.” BC008357 0.59 “HOMO SAPIENS,CLONE IMAGE: 3605655, MRNA” NM_006086 0.59 “HOMO SAPIENS TUBULIN, BETA,4 (TUBB4), MRNA.” NM_014502 0.59 “HOMO SAPIENS NUCLEAR MATRIX PROTEINNMP200 RELATED TO SPLICING FACTOR PRP19 (NMP200), MRNA.” NM_001614 0.59“HOMO SAPIENS ACTIN, GAMMA 1 (ACTG1), MRNA” NM_030753 0.59 “HOMO SAPIENSWINGLESS-TYPE MMTV INTEGRATION SITE FAMILY, MEMBER 3 (WNT3), MRNA”NM_001345 0.59 “HOMO SAPIENS DIACYLGLYCEROL KINASE, ALPHA (80 KD)(DGKA), MRNA.” NM_014824 0.59 “HOMO SAPIENS KIAA0769 GENE PRODUCT(KIAA0769), MRNA.” AF288992 0.59 “HOMO SAPIENS 15 KDA SELENOPROTEIN(SEP15) GENE, COMPLETE CDS” AK025134 0.59 “HOMO SAPIENS CDNA: FLJ21481FIS, CLONE COL05066” NM_001387 0.59 “HOMO SAPIENSDIHYDROPYRIMIDINASE-LIKE 3 (DPYSL3), MRNA.” AY074491 0.59 “HOMO SAPIENSEEG1S (EEG1) MRNA, COMPLETE CDS; ALTERNATIVELY SPLICED” 1138110.2 0.59NULL NM_018647 0.59 “HOMO SAPIENS TUMOR NECROSIS FACTOR RECEPTORSUPERFAMILY, MEMBER 19 (TNFRSFI9), MRNA” NM_012124 0.59 “HOMO SAPIENSCYSTEINE AND HISTIDINE-RICH DOMAIN (CHORD)- CONTAINING, ZINC BINDINGPROTEIN 1 (CHORDC1), MRNA.” NM_005139 0.59 “HOMO SAPIENS ANNEXIN A3(ANXA3), MRNA.” NM_004964 0.59 “HOMO SAPIENS HISTONE DEACETYLASE 1(HDAC1), MRNA.” Y00815 0.59 HUMAN MRNA FOR LCA-HOMOLOG. LAR PROTEIN(LEUKOCYTE ANTIGEN RELATED) NM_006336 0.59 “HOMO SAPIENS ZYG HOMOLOG(ZYG), MRNA.” X15804 0.59 HUMAN MRNA FOR ALPHA-ACTININ AK021570 0.59“HOMO SAPIENS CDNA FLJ11508 FIS, CLONE HEMBA1002162” X69654 0.59 H.SAPIENS MRNA FOR RIBOSOMAL PROTEIN S26 NM_025085 0.59 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ13340 (FLJ13340), TRANSCRIPT VARIANT 2, MRNA”AJ251973 0.59 HOMO SAPIENS PARTIAL STEERIN-1 GENE NM_005936 0.59 “HOMOSAPIENS MYELOID/LYMPHOID OR MIXED-LINEAGE LEUKEMIA (TRITHORAX HOMOLOG,DROSOPHILA); TRANSLOCATED TO, 4 (MLLT4), MRNA” NM_001216 0.59 “HOMOSAPIENS CARBONIC ANHYDRASE IX (CA9), MRNA.” NM_005560 0.60 “HOMO SAPIENSLAMININ, ALPHA 5 (LAMA5), MRNA” NM_018227 0.60 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ10808 (FLJ10808), MRNA.” NM_007355 0.60 “HOMOSAPIENS HEAT SHOCK 90 KD PROTEIN 1, BETA (HSPCB), MRNA.” NM_003657 0.60“HOMO SAPIENS BREAST CARCINOMA AMPLIFIED SEQUENCE 1 (BCAS1), MRNA.”NM_003107 0.60 “HOMO SAPIENS SRY (SEX DETERMINING REGION Y)-BOX 4(SOX4), MRNA.” NM_020665 0.60 “HOMO SAPIENS KIDNEY-SPECIFIC MEMBRANEPROTEIN (NX-17), MRNA.” AB033025 0.60 “HOMO SAPIENS MRNA FOR KIAA1199PROTEIN, PARTIAL CDS” NM_014330 0.60 “HOMO SAPIENS PROTEIN PHOSPHATASE1, REGULATORY (INHIBITOR) SUBUNIT 15A (PPP1R15A), MRNA” NM_001946 0.60“HOMO SAPIENS DUAL SPECIFICITY PHOSPHATASE 6 (DUSP6), TRANSCRIPT VARIANT1, MRNA” NM_031449 0.60 “HOMO SAPIENS KIAA1886 PROTEIN (DKFZP761I2123),MRNA.” AK023110 0.60 “HOMO SAPIENS CDNA FLJ13048 FIS, CLONENT2RP3001399, WEAKLY SIMILAR TO SSU72 PROTEIN” NM_018669 0.60 “HOMOSAPIENS WD REPEAT DOMAIN 4 (WDR4), TRANSCRIPT VARIANT 1, MRNA” NM_0326490.60 “HOMO SAPIENS GLUTAMATE CARBOXYPEPTIDASE-LIKE PROTEIN 2 (CPGL2),MRNA” AL122071 0.60 HOMO SAPIENS MRNA; CDNA DKFZP434H1235 (FROM CLONEDKFZP434H1235); PARTIAL CDS NM_004672 0.60 “HOMO SAPIENSMITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 6 (MAP3K6), MRNA”AF085987 0.60 HOMO SAPIENS FULL LENGTH INSERT CDNA CLONE YU05C01NM_030970 0.60 “HOMO SAPIENS HYPOTHETICAL PROTEIN MGC3771 (MGC3771),MRNA” AL137721 0.60 HOMO SAPIENS MRNA; CDNA DKFZP761H221 (FROM CLONEDKFZP761H221) NM_006282 0.60 “HOMO SAPIENS SERINE/THREONINE KINASE 4(STK4), MRNA” AK023905 0.60 “HOMO SAPIENS CDNA FLJ13843 FIS, CLONETHYRO1000796” BC021898 0.60 “HOMO SAPIENS, CLONE MGC: 17284 IMAGE:4340257, MRNA, COMPLETE CDS” M92843 0.60 “H. SAPIENS ZINC FINGERTRANSCRIPTIONAL REGULATOR MRNA, COMPLETE CDS” NM_002276 0.60 “HOMOSAPIENS KERATIN 19 (KRT19), MRNA” NM_004363 0.60 “HOMO SAPIENSCARCINOEMBRYONIC ANTIGEN-RELATED CELL ADHESION MOLECULE 5 (CEACAM5),MRNA” NM_002273 0.61 “HOMO SAPIENS KERATIN 8 (KRT8), MRNA” BF663771 0.61602145203F1 HOMO SAPIENS CDNA 5′ END M14333 0.61 “GNL|UG|HS#S341910 HOMOSAPIENS C-SYN PROTOONCOGENE MRNA, COMPLETE CDS/CDS = (579, 2192)/GB =M14333/GI = 181171/UG = HS.169370/ LEN = 2647” NM_033292 0.61 “HOMOSAPIENS CASPASE 1, APOPTOSIS-RELATED CYSTEINE PROTEASE (INTERLEUKIN 1,BETA, CONVERTASE) (CASP1), TRANSCRIPT VARIANT ALPHA, MRNA.” BC0036410.61 “HOMO SAPIENS, CLONE MGC: 4645 IMAGE: 3529568, MRNA, COMPLETE CDS”NM_030760 0.61 “HOMO SAPIENS ENDOTHELIAL DIFFERENTIATION, SPHINGOLIPIDG-PROTEIN- COUPLED RECEPTOR, 8 (EDG8), MRNA” BC003693 0.61 “HOMOSAPIENS, SIMILAR TO RIKEN CDNA 3930401K13 GENE, CLONE IMAGE: 3454556,MRNA, PARTIAL CDS” NM_000930 0.61 “HOMO SAPIENS PLASMINOGEN ACTIVATOR,TISSUE (PLAT), TRANSCRIPT VARIANT 1, MRNA” NM_018096 0.61 “HOMO SAPIENSHYPOTHETICAL PROTEIN SIMILAR TO BETA-TRANSDUCIN FAMILY (FLJ10458),MRNA.” NM_001240 0.61 “HOMO SAPIENS CYCLIN T1 (CCNT1), MRNA.” NM_0012990.61 “HOMO SAPIENS CALPONIN 1, BASIC, SMOOTH MUSCLE (CNN1), MRNA”NM_001621 0.61 “HOMO SAPIENS ARYL HYDROCARBON RECEPTOR (AHR), MRNA.”NM_005082 0.61 “HOMO SAPIENS ZINC FINGER PROTEIN 147(ESTROGEN-RESPONSIVE FINGER PROTEIN) (ZNF147), MRNA.” NM_004845 0.61“HOMO SAPIENS PHOSPHATE CYTIDYLYLTRANSFERASE 1, CHOLINE, BETA ISOFORM(PCYT1B), MRNA.” NM_003286 0.61 “HOMO SAPIENS TOPOISOMERASE (DNA) I(TOP1), MRNA.” NM_144660 0.61 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ25082 (FLJ25082), MRNA” NM_004904 0.61 “HOMO SAPIENS CAMP RESPONSEELEMENT-BINDING PROTEIN CRE-BPA (H_GS165L15.1), MRNA” AB033075 0.61“HOMO SAPIENS MRNA FOR KIAA1249 PROTEIN, PARTIAL CDS” NM_020239 0.61“HOMO SAPIENS SMALL PROTEIN EFFECTOR 1 OF CDC42 (SPEC1), MRNA” NM_0059020.61 “HOMO SAPIENS MAD, MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 3(DROSOPHILA) (MADH3), MRNA” NM_014296 0.61 “HOMO SAPIENS CALPAIN 7(CAPN7), MRNA.” NM_025049 0.61 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ22692 (FLJ22692), MRNA” NM_001674 0.61 “HOMO SAPIENS ACTIVATINGTRANSCRIPTION FACTOR 3 (ATF3), MRNA” NM_021960 0.61 “HOMO SAPIENSMYELOID CELL LEUKEMIA SEQUENCE 1 (BCL2-RELATED) (MCL1), MRNA” NM_0244980.61 “HOMO SAPIENS ZINC FINGER PROTEIN 117 (HPF9) (ZNF117), MRNA”NM_018006 0.61 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ10140 (FLJ10140),MRNA” NM_001124 0.61 “HOMO SAPIENS ADRENOMEDULLIN (ADM), MRNA.”NM_016377 0.61 “HOMO SAPIENS A KINASE (PRKA) ANCHOR PROTEIN 7 (AKAP7),MRNA.” AK026965 0.61 “HOMO SAPIENS CDNA: FLJ23312 FIS, CLONE HEP11874”NM_031944 0.61 “HOMO SAPIENS MIX-LIKE HOMEOBOX PROTEIN 1 (MILD1), MRNA”AK023426 0.61 “HOMO SAPIENS CDNA FLJ13364 FIS, CLONE PLACE1000292”NM_058189 0.61 “HOMO SAPIENS CHROMOSOME 21 OPEN READING FRAME 69(C21ORF69), MRNA” 1502211.1 0.61 NULL NM_023008 0.62 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ12949 (FLJ12949), MRNA” NM_004706 0.62 “HOMOSAPIENS RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF) 1 (ARHGEF1), MRNA.”NM_001619 0.62 “HOMO SAPIENS ADRENERGIC, BETA, RECEPTOR KINASE 1(ADRBK1), MRNA” NM_003952 0.62 “HOMO SAPIENS RIBOSOMAL PROTEIN S6KINASE, 70 KD, POLYPEPTIDE 2 (RPS6KB2), MRNA.” NM_003407 0.62 “HOMOSAPIENS ZINC FINGER PROTEIN 36, C3H TYPE, HOMOLOG (MOUSE) (ZFP36),MRNA.” 1400651.5 0.62 NULL NM_013275 0.62 “HOMO SAPIENS NASOPHARYNGEALCARCINOMA SUSCEPTIBILITY PROTEIN (LZ16), MRNA.” X62006 0.62 H. SAPIENSPTB-1 GENE FOR POLYPIRIMIDINE TRACT BINDING PROTEIN NM_001949 0.62 “HOMOSAPIENS E2F TRANSCRIPTION FACTOR 3 (E2F3) MRNA, COMPLETE CDS.” NM_1450060.62 “HOMO SAPIENS HYPOTHETICAL PROTEIN MGC26847 (MGC26847), MRNA”NM_145252 0.62 “HOMO SAPIENS SIMILAR TO COMMON SALIVARY PROTEIN 1(LOC124220), MRNA” NM_003414 0.62 “HOMO SAPIENS ZINC FINGER PROTEIN 267(ZNF267), TRANSCRIPT VARIANT 498723, MRNA.” NM_017818 0.62 “HOMO SAPIENSWD REPEAT DOMAIN 8 (WDR8), MRNA.” NM_022343 0.62 “HOMO SAPIENSCHROMOSOME 9 OPEN READING FRAME 19 (C9ORF19), MRNA” AL163305 0.62 NULLNM_016014 0.62 “HOMO SAPIENS CGI-67 PROTEIN (LOC51104), MRNA.” NM_0059690.62 “HOMO SAPIENS NUCLEOSOME ASSEMBLY PROTEIN 1-LIKE 4 (NAP1L4), MRNA.”NM_002939 0.62 “HOMO SAPIENS RIBONUCLEASE/ANGIOGENIN INHIBITOR (RNH),MRNA.” 101314.1 0.62 NULL NM_016123 0.62 “HOMO SAPIENS PUTATIVE PROTEINKINASE NY-REN-64 ANTIGEN (LOC51135), MRNA.” NM_016265 0.62 “HOMO SAPIENSGIOT-3 FOR GONADOTROPIN INDUCIBLE TRANSCRIPTION REPRESSOR-3 (GIOT-3),MRNA.” NM_032873 0.62 “HOMO SAPIENS NM23-PHOSPHORYLATED UNKNOWNSUBSTRATE (MGC15437), MRNA” NM_030575 0.62 “HOMO SAPIENS HYPOTHETICALPROTEIN MGC10334 (MGC10334), MRNA.” NM_032678 0.62 “HOMO SAPIENSHYPOTHETICAL PROTEIN MGC3413 (MGC3413), MRNA” AF025772 0.62 “HOMOSAPIENS C2H2 ZINC FINGER PROTEIN (ZNF189) GENE, ALTERNATIVE SPLICEPRODUCTS, COMPLETE CDS” AK025461 0.62 “HOMO SAPIENS CDNA: FLJ21808 FIS,CLONE HEP00851, HIGHLY SIMILAR TO AF151843 HOMO SAPIENS CGI-85 PROTEINMRNA” NM_001461 0.62 “HOMO SAPIENS FLAVIN CONTAINING MONOOXYGENASE 5(FMO5), MRNA.” AK027136 0.62 “HOMO SAPIENS CDNA: FLJ23483 FIS, CLONEKAIA04052” NM_003683 0.62 “HOMO SAPIENS DNA SEGMENT ON CHROMOSOME 21(UNIQUE) 2056 EXPRESSED SEQUENCE (D21S2056E), MRNA.” NM_004218 0.62“HOMO SAPIENS RAB11B, MEMBER RAS ONCOGENE FAMILY (RAB11B), MRNA”NM_004207 0.62 “HOMO SAPIENS SOLUTE CARRIER FAMILY 16 (MONOCARBOXYLICACID TRANSPORTERS), MEMBER 3 (SLC16A3), MRNA.” NM_006781 0.62 “HOMOSAPIENS CHROMOSOME 6 OPEN READING FRAME 10 (C6ORF10), MRNA.” AF0750190.62 HOMO SAPIENS FULL LENGTH INSERT CDNA YI29A01 NM_012319 0.62 “HOMOSAPIENS LIV-1 PROTEIN, ESTROGEN REGULATED (LIV-1), MRNA.” NM_004447 0.62“HOMO SAPIENS EPIDERMAL GROWTH FACTOR RECEPTOR PATHWAY SUBSTRATE 8(EPS8), MRNA.” NM_024616 0.62 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ23186 (FLJ23186), MRNA” NM_004766 0.62 “HOMO SAPIENS COATOMER PROTEINCOMPLEX, SUBUNIT BETA 2 (BETA PRIME) (COPB2), MRNA.” NM_005735 0.62“HOMO SAPIENS ARP1 ACTIN-RELATED PROTEIN 1 HOMOLOG B, CENTRACTIN BETA(YEAST) (ACTR1B), MRNA.” BC007722 0.62 “HOMO SAPIENS, GLYCYL-TRNASYNTHETASE, CLONE MGC: 12625 IMAGE: 4299853, MRNA, COMPLETE CDS”NM_016076 0.62 “HOMO SAPIENS CGI-146 PROTEIN (LOC51029), MRNA.”NM_018226 0.62 “HOMO SAPIENS ARGINYL AMINOPEPTIDASE (AMINOPEPTIDASEB)-LIKE 1 (RNPEPL1), MRNA.” NM_015995 0.63 “HOMO SAPIENS KRUPPEL-LIKEFACTOR 13 (KLF13), MRNA.” NM_001647 0.63 “HOMO SAPIENS APOLIPOPROTEIN D(APOD), MRNA” BQ720870 0.63 AGENCOURT_8296718 HOMO SAPIENS CDNA 5′ ENDNM_002850 0.63 “HOMO SAPIENS PROTEIN TYROSINE PHOSPHATASE, RECEPTORTYPE, S (PTPRS), MRNA.” AK024447 0.63 “HOMO SAPIENS MRNA FOR FLJ00037PROTEIN, PARTIAL CDS” NM_019058 0.63 “HOMO SAPIENS HIF-1 RESPONSIVERTP801 (RTP801), MRNA” BC016029 0.63 “HOMO SAPIENS, CLONE MGC: 16974IMAGE: 3921313, MRNA, COMPLETE CDS” BI906953 0.63 “HUMAN ERK5 MRNA,COMPLETE CDS.” NM_030578 0.63 “HOMO SAPIENS HYPOTHETICAL PROTEIN MGC4093(MGC4093), MRNA” AB011539 0.63 “HOMO SAPIENS MRNA FOR MEGF6 PROTEIN(KIAA0815), PARTIAL CDS” NM_003995 0.63 “HOMO SAPIENS NATRIURETICPEPTIDE RECEPTOR B/GUANYLATE CYCLASE B (ATRIONATRIURETIC PEPTIDERECEPTOR B) (NPR2), MRNA.” U24152 0.63 “P21 ACTIVATED KINASE 1, ASERINE-THREONINE KINASE THAT IS ACTIVATED BY THE RHO-RELATED GTPASESCDC42 AND RAC1, INVOLVED IN REGULATION OF MAP KINASE CASCADES,CYTOSKELETAL CHANGES ASSOCIATED WITH CELL POLARITY AND MIGRATION, ANDINHIBITION OF APOPTOSIS” 331232.27 0.63 “ERYTHROCYTE MEMBRANE PROTEINBAND 4.9 (DEMATIN), A MEMBER OF THE VILLIN SUPERFAMILY, BINDS ANDBUNDLES ACTIN, MAY CONTROL CELL SHAPE AND SIZE, MAY BE INVOLVED INPROSTATE TUMORIGENESIS” 1502800.17 0.63 “PROTEIN OF UNKNOWN FUNCTION,HAS LOW SIMILARITY TO UNCHARACTERIZED C. ELEGANS F08G12.1” NM_0190630.63 “HOMO SAPIENS CHROMOSOME 2 OPEN READING FRAME 2 (C2ORF2), MRNA.”NM_006391 0.63 “HOMO SAPIENS RAN BINDING PROTEIN 7 (RANBP7), MRNA”NM_005572 0.63 “HOMO SAPIENS LAMIN A/C (LMNA), MRNA” NM_004403 0.63“HOMO SAPIENS DEAFNESS, AUTOSOMAL DOMINANT 5 (DFNA5), MRNA.” AK0257030.63 “HOMO SAPIENS CDNA: FLJ22050 FIS, CLONE HEP09454” BC022091 0.63“HOMO SAPIENS, SIMILAR TO SIDEROFLEXIN 2, CLONE MGC: 4567 IMAGE:3029622, MRNA, COMPLETE CDS” NM_018294 0.63 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ10998 (FLJ10998), MRNA.” NM_032179 0.63 “HOMO SAPIENSHYPOTHETICAL PROTEIN FLJ20542 (FLJ20542), MRNA.” NM_002670 0.63 “HOMOSAPIENS PLASTIN 1 (I ISOFORM) (PLS1), MRNA.” NM_025019 0.63 “HOMOSAPIENS LIKELY ORTHOLOG OF MOUSE TUBULIN ALPHA 4 (FLJ13940), MRNA”NM_005962 0.63 “HOMO SAPIENS MAX INTERACTING PROTEIN 1 (MXI1), MRNA.”AF079099 0.63 “HOMO SAPIENS ARGININE-TRNA-PROTEIN TRANSFERASE 1-2P(ATE1) MRNA, ALTERNATIVELY SPLICED PRODUCT, PARTIAL CDS” NM_152905 0.63“HOMO SAPIENS NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLYDOWN-REGULATED 1 (NEDD1), MRNA” NM_012329 0.63 “HOMO SAPIENS MONOCYTE TOMACROPHAGE DIFFERENTIATION- ASSOCIATED (MMD), MRNA.” NM_016428 0.63“HOMO SAPIENS NESH PROTEIN (NESH), MRNA.” NM_033490 0.63 “HOMO SAPIENSCELL DIVISION CYCLE 2-LIKE 1 (PITSLRE PROTEINS) (CDC2L1), TRANSCRIPTVARIANT 6, MRNA” AK021583 0.63 “HOMO SAPIENS CDNA FLJ11521 FIS, CLONEHEMBA1002486” NM_031991 0.63 “HOMO SAPIENS POLYPYRIMIDINE TRACT BINDINGPROTEIN (HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN I) (PTB), TRANSCRIPTVARIANT 3, MRNA.” AL137663 0.63 HOMO SAPIENS MRNA; CDNA DKFZP434G227(FROM CLONE DKFZP434G227) AK056644 0.63 “HOMO SAPIENS CDNA FLJ32082 FIS,CLONE OCBBF2000231, WEAKLY SIMILAR TO PHOSPHOLIPASE A2 INHIBITOR SUBUNITB PRECURSOR” NM_032587 0.63 “HOMO SAPIENS CASPASE RECRUITMENT DOMAINFAMILY, MEMBER 6 (CARD6), MRNA” NM_002115 0.63 “HOMO SAPIENS HEXOKINASE3 (WHITE CELL) (HK3), NUCLEAR GENE ENCODING MITOCHONDRIAL PROTEIN,MRNA.” NM_024677 0.64 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ14001(FLJ14001), MRNA” NM_016262 0.64 “HOMO SAPIENS EPSILON-TUBULIN(LOC51175), MRNA.” NM_024595 0.64 “HOMO SAPIENS HYPOTHETICAL PROTEINFLJ12666 (FLJ12666), MRNA” AB023211 0.64 “HOMO SAPIENS MRNA FOR KIAA0994PROTEIN, PARTIAL CDS” NM_001902 0.64 “HOMO SAPIENS CYSTATHIONASE(CYSTATHIONINE GAMMA-LYASE) (CTH), MRNA.” NM_004593 0.64 “HOMO SAPIENSSPLICING FACTOR, ARGININE/SERINE-RICH 10 (TRANSFORMER 2 HOMOLOG,DROSOPHILA) (SFRS10), MRNA.” NM_007114 0.64 “HOMO SAPIENS TATA ELEMENTMODULATORY FACTOR 1 (TMF1), MRNA.” AK057059 0.64 “HOMO SAPIENS CDNAFLJ32497 FIS, CLONE SKNSH2000250, HIGHLY SIMILAR TO R. NORVEGICUS MRNAFOR K+ CHANNEL PROTEIN, BETA SUBUNIT” NM_016120 0.64 “HOMO SAPIENSPUTATIVE RING ZINC FINGER PROTEIN NY-REN-43 ANTIGEN (LOC51132), MRNA.”AL122046 0.64 HOMO SAPIENS MRNA; CDNA DKFZP434O0515 (FROM CLONEDKFZP434O0515) BQ430788 0.64 AGENCOURT_7776027 HOMO SAPIENS CDNA 5′ ENDNM_000641 0.64 “HOMO SAPIENS INTERLEUKIN 11 (IL11), MRNA” NM_145241 0.64“HOMO SAPIENS SIMILAR TO SPERMATID WD-REPEAT PROTEIN (LOC114987), MRNA”NM_000287 0.64 “HOMO SAPIENS PEROXISOMAL BIOGENESIS FACTOR 6 (PEX6),MRNA.” L47234 0.64 “HOMO SAPIENS ERCC2 (ERCC2) AND KINESIN LIGHT CHAIN(KLC2) GENES, COMPLETE CDS, COMPLETE SEQUENCE” X65178 0.64 H. SAPIENSGENE FOR SUBSTANCE P RECEPTOR (EXON 2) BC012155 0.64 “HOMO SAPIENS,CLONE IMAGE: 4561787, MRNA” AE006466 0.64 HOMO SAPIENS 16P13.3 SEQUENCESECTION 5 OF 8 NM_024096 0.64 “HOMO SAPIENS HYPOTHETICAL PROTEIN MGC5627(MGC5627), MRNA” NM_012484 0.64 “HOMO SAPIENS HYALURONAN-MEDIATEDMOTILITY RECEPTOR (RHAMM) (HMMR), TRANSCRIPT VARIANT 1, MRNA” AK0260640.64 “HOMO SAPIENS CDNA: FLJ22411 FIS, CLONE HRC08456” NM_003713 0.64“HOMO SAPIENS PHOSPHATIDIC ACID PHOSPHATASE TYPE 2B (PPAP2B), MRNA.”NM_015437 0.64 “HOMO SAPIENS DKFZP586N0819 PROTEIN (DKFZP586N0819),MRNA” AW328201 0.64 “DR04H10.X1 NIH_MGC_3 HOMO SAPIENS CDNA CLONE IMAGE:2847235 5′, MRNA SEQUENCE” NM_006247 0.64 “HOMO SAPIENS PROTEINPHOSPHATASE 5, CATALYTIC SUBUNIT (PPP5C), MRNA.” AF051160 0.64 “HOMOSAPIENS TYROSINE PHOSPHATASE (PRL-1) GENE, COMPLETE CDS” NM_002184 0.64“HOMO SAPIENS INTERLEUKIN 6 SIGNAL TRANSDUCER (GP130, ONCOSTATIN MRECEPTOR) (IL6ST), MRNA.” AF047690 0.64 “HUMAN ATP-BINDING CASSETTEPROTEIN M-ABC1 MRNA, NUCLEAR GENE ENCODING MITOCHONDRIAL PROTEIN,COMPLETE CDS.” BG564693 0.64 “602589902F1 HOMO SAPIENS CDNA, 5′ END”NM_005239 0.64 “HOMO SAPIENS V-ETS ERYTHROBLASTOSIS VIRUS E26 ONCOGENEHOMOLOG 2 (AVIAN) (ETS2), MRNA” NM_021131 0.64 “HOMO SAPIENS PROTEINPHOSPHATASE 2A, REGULATORY SUBUNIT B′ (PR53) (PPP2R4), MRNA.” NM_0032430.64 “HOMO SAPIENS TRANSFORMING GROWTH FACTOR, BETA RECEPTOR III(BETAGLYCAN, 300 KD) (TGFBR3), MRNA.” BG535739 0.64 602563859F1 HOMOSAPIENS CDNA 5′ END NM_001087 0.64 “HOMO SAPIENS ANGIO-ASSOCIATED,MIGRATORY CELL PROTEIN (AAMP), MRNA.” NM_019011 0.64 “HOMO SAPIENSTRIAD3 PROTEIN (TRIAD3), MRNA.” NM_005660 0.64 “HOMO SAPIENS SOLUTECARRIER FAMILY 35 (UDP-GALACTOSE TRANSPORTER), MEMBER 2 (SLC35A2), MRNA”AK024739 0.64 “HOMO SAPIENS CDNA: FLJ21086 FIS, CLONE CAS03272” AK0558530.64 “HOMO SAPIENS CDNA FLJ31291 FIS, CLONE KIDNE2007356” AB010443 0.64“HOMO SAPIENS DNA, DLEC1 TO ORCTL4 GENE REGION, SECTION 1/2 (DLEC1,ORCTL3, ORCTL4 GENES, COMPLETE CDS).” NM_002695 0.64 “HOMO SAPIENSPOLYMERASE (RNA) II (DNA DIRECTED) POLYPEPTIDE E (25 KD) (POLR2E),MRNA.” NM_018304 0.64 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ11029(FLJ11029), MRNA” NM_032484 0.64 “HOMO SAPIENS D11LGP1E-LIKE (LGP1),MRNA” AL832781 0.64 HOMO SAPIENS MRNA; CDNA DKFZP686L057 (FROM CLONEDKFZP686L057) NM_021027 0.64 “HOMO SAPIENS UDP GLYCOSYLTRANSFERASE 1FAMILY, POLYPEPTIDE A9 (UGT1A9), MRNA.” NM_021993 0.64 “HOMO SAPIENS FUSINTERACTING PROTEIN (SERINE-ARGININE RICH) 2 (FUSIP2), MRNA.” NM_0144200.64 “HOMO SAPIENS DICKKOPF HOMOLOG 4 (XENOPUS LAEVIS) (DKK4), MRNA”BC015931 0.64 “HOMO SAPIENS, RAB35, MEMBER RAS ONCOGENE FAMILY, CLONEMGC: 8924 IMAGE: 3907209, MRNA, COMPLETE CDS” NM_006706 0.64 “HOMOSAPIENS TRANSCRIPTION ELONGATION REGULATOR 1 (CA150) (TCERG1), MRNA”AF155117 0.64 “HOMO SAPIENS NY-REN-62 ANTIGEN MRNA, PARTIAL CDS”AB033086 0.65 “HOMO SAPIENS MRNA FOR KIAA1260 PROTEIN, PARTIAL CDS”NM_000666 0.65 “HOMO SAPIENS AMINOACYLASE 1 (ACY1), MRNA.” NM_0529320.65 “HOMO SAPIENS PRO-ONCOSIS RECEPTOR INDUCING MEMBRANE INJURY GENE(PORIMIN), MRNA” NM_005605 0.65 “HOMO SAPIENS PROTEIN PHOSPHATASE 3(FORMERLY 2B), CATALYTIC SUBUNIT, GAMMA ISOFORM (CALCINEURIN A GAMMA)(PPP3CC), MRNA.” BC036771 0.65 “HOMO SAPIENS, CLONE MGC: 46680 IMAGE:5576828, MRNA, COMPLETE CDS” NM_000433 0.65 “HOMO SAPIENS NEUTROPHILCYTOSOLIC FACTOR 2 (65 KD, CHRONIC GRANULOMATOUS DISEASE, AUTOSOMAL 2)(NCF2), MRNA.” NM_007198 0.65 “HOMO SAPIENS PROLINE SYNTHETASECO-TRANSCRIBED HOMOLOG (BACTERIAL) (PROSC), MRNA” AB028645 0.65 “HOMOSAPIENS MRNA FOR CBL-C, COMPLETE CDS” NM_004040 0.65 “HOMO SAPIENS RASHOMOLOG GENE FAMILY, MEMBER B (ARHB), MRNA” AK096820 0.65 “HOMO SAPIENSCDNA FLJ39501 FIS, CLONE PROST2016980, MODERATELY SIMILAR TO CYTOCHROMEP450 4F2 (EC 1.14.13.30)” NM_007054 0.65 “HOMO SAPIENS KINESIN FAMILYMEMBER 3A (KIF3A), MRNA.” NM_002227 0.65 “HOMO SAPIENS JANUS KINASE 1 (APROTEIN TYROSINE KINASE) (JAK1), MRNA.” NM_030674 0.65 “HOMO SAPIENSAMINO ACID TRANSPORTER SYSTEM A1 (ATA1), MRNA.” AB025432 0.65 “HOMOSAPIENS MRNA FOR GILZ, COMPLETE CDS” NM_015945 0.65 “HOMO SAPIENSOVARIAN CANCER OVEREXPRESSED 1 (OVCOV1), MRNA” BC012362 0.65 “HOMOSAPIENS, CLONE MGC: 20484 IMAGE: 4650072, MRNA, COMPLETE CDS” NM_0209930.65 “HOMO SAPIENS B-CELL CLL/LYMPHOMA 7A (BCL7A), MRNA” NM_032219 0.65“HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ22269 (FLJ22269), MRNA.” NM_0246040.65 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ21908 (FLJ21908), MRNA”NM_004203 0.65 “HOMO SAPIENS MEMBRANE-ASSOCIATED TYROSINE- ANDTHREONINE- SPECIFIC CDC2-INHIBITORY KINASE (PKMYT1), MRNA” NM_0059790.65 “HOMO SAPIENS S100 CALCIUM BINDING PROTEIN A13 (S100A13), MRNA.”1075733.1 0.65 NULL BG678787 0.65 602624339F1 HOMO SAPIENS CDNA 5′ ENDAK021872 0.65 “HOMO SAPIENS CDNA FLJ11810 FIS, CLONE HEMBA1006347,MODERATELY SIMILAR TO MALES-ABSENT ON THE FIRST PROTEIN (EC 2.3.1.—)”NM_022114 0.65 “HOMO SAPIENS PR DOMAIN CONTAINING 16 (PRDM16), MRNA”NM_002834 0.65 “HOMO SAPIENS PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTORTYPE 11 (PTPN11), TRANSCRIPT VARIANT 1, MRNA” NM_003468 0.65 “HOMOSAPIENS FRIZZLED HOMOLOG 5 (DROSOPHILA) (FZD5), MRNA” NM_016022 0.65“HOMO SAPIENS CGI-78 PROTEIN (LOC51107), MRNA.” BC001096 0.65 “HOMOSAPIENS, CLONE IMAGE: 3507281, MRNA, PARTIAL CDS” NM_032769 0.65 “HOMOSAPIENS HYPOTHETICAL PROTEIN MGC16212 (MGC16212), MRNA” AF118108 0.65“HOMO SAPIENS LYMPHATIC ENDOTHELIUM-SPECIFIC HYALURONAN RECEPTOR LYVE-1MRNA, COMPLETE CDS” NM_005276 0.65 “HOMO SAPIENS GLYCEROL-3-PHOSPHATEDEHYDROGENASE 1 (SOLUBLE) (GPD1), MRNA” NM_015621 0.65 “HOMO SAPIENSDKFZP434C171 PROTEIN (DKFZP434C171), MRNA.” NM_004749 0.65 “HOMO SAPIENSCELL CYCLE PROGRESSION 2 PROTEIN (CPR2), MRNA.” AF088062 0.65 HOMOSAPIENS FULL LENGTH INSERT CDNA CLONE ZD74E10 1082602.1 0.65 “PROTEINWITH HIGH SIMILARITY TO ZINC-FINGER PROTEIN (HUMAN ZNF10), WHICHINHIBITS SOME COMPONENTS OF RNA POLYMERASE II AND III TRANSCRIPTION,CONTAINS FIFTEEN C2H2 TYPE ZINC FINGER DOMAINS, WHICH BIND NUCLEICACIDS” AF037448 0.65 “HOMO SAPIENS RRM RNA BINDING PROTEIN GRY-RBP(GRY-RBP) MRNA, COMPLETE CDS” NM_030792 0.65 “HOMO SAPIENS HYPOTHETICALPROTEIN PP1665 (PP1665), MRNA” AF113511 0.65 “HOMO SAPIENS INTEGRINSUBUNIT ALPHA-2 (ITGA2) GENE, ITGA2-2 ALLELE, 3′UTR” NM_005433 0.65“HOMO SAPIENS V-YES-1 YAMAGUCHI SARCOMA VIRAL ONCOGENE HOMOLOG 1 (YES1),MRNA.” NM_020123 0.65 “HOMO SAPIENS ENDOMEMBRANE PROTEIN EMP70 PRECURSORISOLOG (LOC56889), MRNA.” AP000500 0.65 “HOMO SAPIENS GENOMIC DNA,CHROMOSOME 3P21.3, CLONE: 603 TO 320, ANTI-ONCOGENE REGION, SECTION 3/3”BC012170 0.65 “HOMO SAPIENS, SIMILAR TO RIKEN CDNA 6230427J02 GENE,CLONE MGC: 20416 IMAGE: 4642270, MRNA, COMPLETE CDS” D50683 0.65 “HOMOSAPIENS MRNA FOR TGF-BETAIIR ALPHA, COMPLETE CDS” NM_003236 0.65 “HOMOSAPIENS TRANSFORMING GROWTH FACTOR, ALPHA (TGFA), MRNA.” AB058760 0.65“HOMO SAPIENS MRNA FOR KIAA1857 PROTEIN, PARTIAL CDS” BM724842 0.65“UI-E-EJ0-AIS-H-20-0-UI.R1 HOMO SAPIENS CDNA, 5′ END” NM_003244 0.65“HOMO SAPIENS TGFB-INDUCED FACTOR (TALE FAMILY HOMEOBOX) (TGIF), MRNA.”NM_018986 0.65 “HOMO SAPIENS HYPOTHETICAL PROTEIN (FLJ20356), MRNA.”NM_016629 0.65 “HOMO SAPIENS HYPOTHETICAL PROTEIN (LOC51323), MRNA.”NM_005787 0.65 “HOMO SAPIENS NOT56 (D. MELANOGASTER)-LIKE PROTEIN(NOT56L), MRNA.” NM_004357 0.65 “HOMO SAPIENS CD151 ANTIGEN (CD151),TRANSCRIPT VARIANT 1, MRNA” NM_144643 0.65 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ30655 (FLJ30655), MRNA” BC018130 0.65 “HOMO SAPIENS,COAGULATION FACTOR II (THROMBIN) RECEPTOR-LIKE 1, CLONE MGC: 9298 IMAGE:3895653, MRNA, COMPLETE CDS” NM_000426 0.65 “HOMO SAPIENS LAMININ, ALPHA2 (MEROSIN, CONGENITAL MUSCULAR DYSTROPHY) (LAMA2), MRNA.” AK024835 0.65“HOMO SAPIENS CDNA: FLJ21182 FIS, CLONE CAS11560, HIGHLY SIMILAR TOD83735 HOMO SAPIENS MRNA FOR NEUTRAL CALPONIN” NM_007034 0.65 “HOMOSAPIENS DNAJ (HSP40) HOMOLOG, SUBFAMILY B, MEMBER 4 (DNAJB4), MRNA.”BQ430527 0.66 AGENCOURT_7723632 HOMO SAPIENS CDNA 5′ END NM_015533 0.66“HOMO SAPIENS DKFZP586B1621 PROTEIN (DKFZP586B1621), MRNA” NM_0063860.66 “HOMO SAPIENS DEAD/H (ASP-GLU-ALA-ASP/HIS) BOX POLYPEPTIDE 17 (72KD) (DDX17), TRANSCRIPT VARIANT 1, MRNA.” NM_004417 0.66 “HOMO SAPIENSDUAL SPECIFICITY PHOSPHATASE 1 (DUSP1), MRNA.” NM_002350 0.66 “HOMOSAPIENS V-YES-1 YAMAGUCHI SARCOMA VIRAL RELATED ONCOGENE HOMOLOG (LYN),MRNA.” AK024950 0.66 “HOMO SAPIENS CDNA: FLJ21297 FIS, CLONE COL02035”NM_001283 0.66 “HOMO SAPIENS ADAPTOR-RELATED PROTEIN COMPLEX 1, SIGMA 1SUBUNIT (AP1S1), TRANSCRIPT VARIANT 1, MRNA.” NM_004387 0.66 “HOMOSAPIENS CARDIAC-SPECIFIC HOMEO BOX (CSX), MRNA.” NM_013311 0.66 “HOMOSAPIENS INSULIN PROMOTER FACTOR 1, HOMEODOMAIN TRANSCRIPTION FACTOR(IPF1), MRNA” NM_014604 0.66 “HOMO SAPIENS TAX INTERACTION PROTEIN 1(TIP-1), MRNA” AJ229040 0.66 HOMO SAPIENS 959 KB CONTIG BETWEEN AML1 ANDCBR1 ON CHROMOSOME 21Q22 AL117595 0.66 HOMO SAPIENS MRNA; CDNADKFZP564C2063 (FROM CLONE DKFZP564C2063) NM_005384 0.66 “HOMO SAPIENSNUCLEAR FACTOR, INTERLEUKIN 3 REGULATED (NFIL3), MRNA.” AK024490 0.66“HOMO SAPIENS MRNA FOR FLJ00092 PROTEIN, PARTIAL CDS” NM_016084 0.66“HOMO SAPIENS RAS, DEXAMETHASONE-INDUCED 1 (RASD1), MRNA.” NM_0049990.66 “HOMO SAPIENS MYOSIN VI (MYO6), MRNA.” NM_006844 0.66 “HOMO SAPIENSILVB (BACTERIAL ACETOLACTATE SYNTHASE)-LIKE (ILVBL), MRNA.” NM_0180150.66 “HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ10178 (FLJ10178), MRNA”NM_032287 0.66 “HOMO SAPIENS HYPOTHETICAL PROTEIN DKFZP761O17121(DKFZP761O17121), MRNA.” U32642 0.66 “HUMAN H4 GENE, INTRON 1, PARTIALSEQUENCE” NM_080385 0.66 “HOMO SAPIENS CARBOXYPEPTIDASE A5 (CPA5), MRNA”AF132811 0.66 “HOMO SAPIENS NECTIN-LIKE PROTEIN 2 (NECL2) MRNA, COMPLETECDS” U09847 0.66 “HUMAN ZINC FINGER PROTEIN (ZNF138) MRNA, PARTIAL CDS”NM_014770 0.66 “HOMO SAPIENS CENTAURIN, GAMMA 1 (CENTG1), MRNA”NM_016016 0.66 “HOMO SAPIENS CGI-69 PROTEIN (LOC51629), MRNA” NM_0040990.66 “HOMO SAPIENS ERYTHROCYTE MEMBRANE PROTEIN BAND 7.2 (STOMATIN)(EPB72), MRNA” NM_018347 0.66 “HOMO SAPIENS CHROMOSOME 20 OPEN READINGFRAME 29 (C20ORF29), MRNA.” NM_002895 0.66 “HOMO SAPIENSRETINOBLASTOMA-LIKE 1 (P107) (RBL1), MRNA” AB033093 0.66 “HOMO SAPIENSMRNA FOR KIAA1267 PROTEIN, PARTIAL CDS” BC000712 0.66 “HOMO SAPIENS,SIMILAR TO KINESIN FAMILY MEMBER C1, CLONE MGC: 1202 IMAGE: 3506669,MRNA, COMPLETE CDS” NM_003897 0.66 “HOMO SAPIENS IMMEDIATE EARLYRESPONSE 3 (IER3), TRANSCRIPT VARIANT SHORT, MRNA.” NM_018725 0.66 “HOMOSAPIENS INTERLEUKIN 17B RECEPTOR (IL17BR), MRNA” NM_032307 0.66 “HOMOSAPIENS HYPOTHETICAL PROTEIN MGC10999 (MGC10999), MRNA” NM_025008 0.66“HOMO SAPIENS HYPOTHETICAL PROTEIN FLJ13544 (FLJ13544), MRNA” Y143210.66 “HOMO SAPIENS PMP69 GENE, EXONS 8, 9, 10 & 11” NM_024048 0.66 “HOMOSAPIENS HYPOTHETICAL PROTEIN MGC3020 (MGC3020), MRNA” NM_025106 0.66“HOMO SAPIENS SPRY DOMAIN-CONTAINING SOCS BOX PROTEIN SSB-1 (FLJ22393),MRNA.” NM_002906 0.66 “HOMO SAPIENS RADIXIN (RDX), MRNA” NM_152338 0.66“HOMO SAPIENS ZYMOGEN GRANULE PROTEIN 16 (ZG16), MRNA” BC019623 0.66“HOMO SAPIENS, CLONE IMAGE: 4539469, MRNA, PARTIAL CDS” AF218848 0.66“HOMO SAPIENS BETA II SPECTRIN-SHORT ISOFORM MRNA, PARTIAL CDS”NM_006313 0.66 “HOMO SAPIENS UBIQUITIN SPECIFIC PROTEASE 15 (USP15),MRNA.” M92300 0.66 “HUMAN HUMAN VOLTAGE-DEPENDENT CALCIUM CHANNEL BETA-1SUBUNIT, EXONS 1-4” AL163263 0.66 NULL NM_030974 0.66 “HOMO SAPIENSHYPOTHETICAL PROTEIN DKFZP434N1923 (DKFZP434N1923), MRNA” NM_022139 0.66“HOMO SAPIENS GDNF FAMILY RECEPTOR ALPHA 4 (GFRA4), TRANSCRIPT VARIANT1, MRNA” L44140 0.66 “HOMO SAPIENS CHROMOSOME X REGION FROM FILAMIN(FLN) GENE TO GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) GENE, COMPLETECDS′S” M87507 0.66 “HOMO SAPIEN INTERLEUKIN-1 BETA CONVERTASE (IL1BCE)MRNA, COMPLETE CDS” NM_004095 0.66 “HOMO SAPIENS EUKARYOTIC TRANSLATIONINITIATION FACTOR 4E BINDING PROTEIN 1 (EIF4EBP1), MRNA” NM_080678 0.66“HOMO SAPIENS NEDD8-CONJUGATING ENZYME (NCE2), MRNA” NM_007097 0.66“HOMO SAPIENS CLATHRIN, LIGHT POLYPEPTIDE (LCB) (CLTB), MRNA.” NM_0201420.66 “HOMO SAPIENS NADH: UBIQUINONE OXIDOREDUCTASE MLRQ SUBUNIT HOMOLOG(LOC56901), MRNA” NM_012141 0.66 “HOMO SAPIENS DEAD/H(ASP-GLU-ALA-ASP/HIS) BOX POLYPEPTIDE 26 (DDX26), MRNA.” NM_005257 0.66“HOMO SAPIENS GATA BINDING PROTEIN 6 (GATA6), MRNA.” BC002766 0.66 “HOMOSAPIENS, SIMILAR TO KIAA0998 PROTEIN, CLONE MGC: 4173 IMAGE: 3632160,MRNA, COMPLETE CDS” NM_002084 0.66 “HOMO SAPIENS GLUTATHIONE PEROXIDASE3 (PLASMA) (GPX3), MRNA” NM_017855 0.66 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ20513 (FLJ20513), MRNA” AB018353 0.66 “HOMO SAPIENS MRNA FORKIAA0810 PROTEIN, PARTIAL CDS” NM_018475 0.66 “HOMO SAPIENS TPAREGULATED LOCUS (TPARL), MRNA” NM_018078 0.66 “HOMO SAPIENS HYPOTHETICALPROTEIN FLJ10378 (FLJ10378), MRNA” NM_017838 0.66 “HOMO SAPIENSNUCLEOLAR PROTEIN FAMILY A, MEMBER 2 (H/ACA SMALL NUCLEOLAR RNPS)(NOLA2), MRNA.” NM_005475 0.66 “HOMO SAPIENS LYMPHOCYTE ADAPTOR PROTEIN(LNK), MRNA.” NM_002961 0.66 “HOMO SAPIENS S100 CALCIUM BINDING PROTEINA4 (CALCIUM PROTEIN, CALVASCULIN, METASTASIN, MURINE PLACENTAL HOMOLOG)(S100A4), TRANSCRIPT VARIANT 1, MRNA” AL133626 0.67 HOMO SAPIENS MRNA;CDNA DKFZP434K0522 (FROM CLONE DKFZP434K0522) X65644 0.67 H. SAPIENSMRNA MBP-2 FOR MHC BINDING PROTEIN 2 NM_006270 0.67 “HOMO SAPIENSRELATED RAS VIRAL (R-RAS) ONCOGENE HOMOLOG (RRAS), MRNA.” AK001674 0.67“HOMO SAPIENS CDNA FLJ10812 FIS, CLONE NT2RP4000975” NM_001980 0.67“HOMO SAPIENS EPIMORPHIN (EPIM), MRNA.” AF125158 0.67 “HUMAN ZINC FINGERDNA BINDING PROTEIN 99 (ZNF281) MRNA, COMPLETE CDS.” NM_032310 0.67“HOMO SAPIENS HYPOTHETICAL PROTEIN MGC11115 (MGC11115), MRNA” NM_0204230.67 “HOMO SAPIENS HYPOTHETICAL PROTEIN LOC57147 (LOC57147), MRNA”NM_001694 0.67 “HOMO SAPIENS ATPASE, H+ TRANSPORTING, LYSOSOMAL(VACUOLAR PROTON PUMP) 16 KD (ATP6L), MRNA.” NM_014547 0.67 “HOMOSAPIENS TROPOMODULIN 3 (UBIQUITOUS) (TMOD3), MRNA” NM_024874 0.67 “HOMOSAPIENS HYPOTHETICAL PROTEIN FLJ14225 (FLJ14225), MRNA” AF244812 0.67“HOMO SAPIENS SCAN DOMAIN-CONTAINING PROTEIN 2 (SCAND2) GENE, COMPLETECDS, ALTERNATIVELY SPLICED” NM_024070 0.67 “HOMO SAPIENS HYPOTHETICALPROTEIN MGC2463 (MGC2483), MRNA”

1. A method for modulating the farnesoid X receptor, wherein the diseaseto be treated is selected from the group consisting of hypercholestermiaand cholestasis, said method comprising contacting said receptor with aneffective amount of at least one compound having the structure:

wherein: A is a C3 up to C8 branched chain alkyl or substituted alkylgroup, a C3 up to C7 cycloalkyl or substituted cycloalkyl, an optionallysubstituted aryl or an optionally substituted heteroaryl, X is —C(O)— or—CH₂—, R is methyl or ethyl, R¹ is H, hydroxy, alkoxy, benzoyloxy,mesityloxy, or —OCH₂C(O)OC₂H₅, R² is H or R² can cooperate with R³ toform a benzopyran, wherein the pyran ring has the structure:

wherein: R⁶ is not present if the pyran ring is unsaturated, or, ifpresent, is selected from H, —OR, wherein R is alkyl or acyl, or R⁶ cancooperate with R⁷ to form a cyclic acetal, a cyclic ketal, or acyclopropyl moiety, and only one of R⁷ and R⁸ is present if the pyranring is unsaturated, or R⁷ and R⁸ are independently H, carboxyl, cyano,hydroxy, alkoxy, thioalkyl, aryl, or R⁷ and R⁸ taken together comprise acarbonyl oxygen or an oxime nitrogen, or either R⁷ or R⁸ can cooperatewith R⁶ to form a cyclic acetal, a cyclic ketal, or a cyclopropylmoiety, R³ can cooperate with R² to form a benzopyran having thestructure set forth above, or R³ is alkenyl, optionally substituted arylor heteroaryl, or optionally substituted arylalkenyl orheteroarylalkenyl, R⁴ is H or hydroxy, and R⁵ is H, hydroxy, alkoxy oraryloxy.
 2. The method of claim 1 wherein said method comprisestreatment of hypercholestemia.
 3. The method of claim 1 wherein saidmethod comprises treatment of cholestasis.
 4. The method of claim 1wherein R² and R³ cooperate to form a benzopyran.
 5. The method of claim4 wherein A is cyclopropyl, X is —C(O)—, R¹ is methoxy, R⁶ and R⁷ areabsent, and R⁴R⁵ and R⁸ are hydrogen.
 6. The method of claim 4 wherein Ais cyclopropyl, X is —CH₂—, R¹ is methoxy, R⁶ and R⁷ are absent, and R⁴,R⁵ and R⁸ are hydrogen.
 7. The method of claim 4 wherein A iscyclohexyl, X is —C(O)—, R¹ is methoxy, R⁶ and R⁷ are absent, and R⁴, R⁵and R⁸ are hydrogen.
 8. The method of claim 4 wherein A is phenyl, X is—C(O)—, R¹ is methoxy, R⁶ and R⁷ are absent, and R⁴, R⁵ and R⁸ arehydrogen.
 9. The method of claim 4 wherein A is phenyl, X is —O(O)—, R¹is methoxy, R⁶ and R⁷ cooperate to form a dichlorocyclopropyl ring, andR⁴, R⁵ and R⁸ are hydrogen.
 10. The method of claim 4 wherein A iscyclohexyl, X is —C(O)—, R¹ is methoxy, R⁶ and R⁷ cooperate to form adichlorocyclopropyl ring, and R⁴, R⁵ and R⁸ are hydrogen.
 11. The methodof claim 1 wherein R³ is substituted or unsubstituted alkenyl.
 12. Themethod of claim 11 wherein A is cyclohexyl, X is —C(O)—, R¹, R², R⁴ andR⁵ are hydrogen, and R³ is —CH═CH—C(O)—O-tBu.
 13. The method of claim 1wherein R³ is optionally substituted aryl or heteroaryl.
 14. The methodof claim 13 wherein said compound is selected from the group consistingof compounds wherein: A is cyclohexyl, X is —C(O)—, R¹, R², R⁴ and R⁵are each hydrogen, and R³ is selected from the group consisting ofphenyl, p-thiomethyl-phenyl, m-methoxy-phenyl, m-acetyl-phenyl,5-methyl-2-thiophene-yl, 5-acetyl-2-thiophene-yl,4-dimethylamino-phenyl, and 2,3-(O—CH₂—O)-phenyl.
 15. The method ofclaim 13 wherein said compound is selected from the group consisting ofcompounds wherein: A is isopropyl, X is —C(O)—, R¹, R², R⁴ and R⁵ areeach hydrogen, and R³ is 4-dimethylamino-phenyl, or2,3-(O—CH₂—O)-phenyl.
 16. The method of claim 1 wherein R³ is oroptionally substituted arylalkenyl or heteroarylalkenyl.
 17. The methodof claim 16 wherein said compound is selected from the group consistingof compounds wherein: A is cyclohexyl, X is —C(O)—, R¹, R², R⁴ and R⁵are each hydrogen, and R³ is selected from the group consisting of—CH═CH-phenyl, —CH═CH-p-methoxy-phenyl, —CH═CH-o-fluoro-phenyl,—CH═CH-m-fluoro-phenyl, and —CH═CH-p-fluoro-phenyl.
 18. The method ofclaim 16 wherein said compound is selected from the group consisting ofcompounds wherein: A is isopropyl, X is —C(O)—, R¹, R², R⁴ and R⁵ areeach hydrogen, and R³ is selected from the group consisting of—CH═CH-phenyl, —CH═CH-o-fluoro-phenyl, —CH═CH-m-fluoro-phenyl, and—CH═CH-p-fluoro-phenyl.